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The Gelsolin Family

A group of actin binding proteins, sharing  repeats of about 15kDa homologous domains (Way & Weeds, 1988) that adopt a similar fold (Burtnick et al, 1999).  The gelsolins typically sever and cap actin filaments in a Ca2+, pH and phospholipid dependent manner and are involved in cell structure, motility, apoptosis, amyloidosis and cancer.  Gelsolin is a very well studied protein yet surprises continue to be discovered in its structure and its function.  Many proteins exist that show homology to the gelsolins. 

Contents:-

Gelsolin N to C terminus cold to warm colours

Gelsolin: A historical perspective

The importance of "gel" to "sol" transformation in cell motility was appreciated even before the existence of microfilaments were known (de Bruyn, 1947). It was established from microscopic studies that the cytoplasm (protoplasm) of large amoeboid organisms cold exist in a fluid, or a more solid gel-like phase, and that one could produce the other. The dynamic state of the cytosol is the basis for many important cellular processes, from cell locomotion, secretion, cytokinesis and synaptic plasticity.  It is now appreciated that these reversible gel to sol transformation results from the re-organisation of the actin based cytoskeleton. Actually, gel to sol transformation can be accomplished by a number of concomitant events, actin filaments are severed into small fragments that lowers the viscosity, and the actin filaments themselves de-polymerise, and a variety of crosslinking proteins are triggered to loosen their grip of the filaments.  All of the events are modulated or mediated by "actin-binding proteins", that occur in a number varieties.  Gelsolin is an actin binding protein that has many properties that makes it very likely to be primarily involved in all important gel to sol transformations, and has been given its name in recognition of this.  Gelsolin was first identified in macrophages (Yin & Stossel, 1979; 1980) and soon after in platelets (Wang & Bryan, 1981), and in serum (Harris et al, 1980). Gelsolin has also been known as brevin (Harris & Schwartz, 1981) and confusingly "actin depolymering factor" (Harris & Gooch, 1981Norberg et al, 1979), this name has also been given to another group of filament severing/depolymerising proteins of lower molecular weight (see ADF/Cofilins).

 

Gelsolin: Function and Structure
The domain structure of gelsolin.  There are three actin-binding sites (Bryan, 1988) spread across three domains. G1 and G4 Pope et al, 1996 ) bind G-actin, whereas G2 binds F-actin strongly and G-actin 100x less strongly ().  G2 also binds tropomyosin (Koepf & Burtnick 1992; Maciver et al, 2000).  The entire molecule is regulated by PIP2 binding at two sites in G1 and G2.
Click here for a diagram of the domain structure of the whole Gelsolin/Villin family.

Gelsolin is a comparatively large and complicated actin binding protein consisting of six-similar domains that have very different properties.  This complexity of form reflects a complexity of function.  Not only is gelsolin modulated by acidic phospholipids (see Gelsolin and Phospholipids), but it also modulate the metabolism of these lipids that in turn have regulatory effects as mitogenicity of the whole cell (Yin, 1988).  

The family of which gelsolin is a member, may be divided into two groups (Weeds & Maciver, 1993); class I, severing and capping proteins, and the Class II, capping proteins that do not sever. Class II also includes capping proteins that have little or no sequence similarity to the gelsolin group. The class I group consist of either six (gelsolin, villin) or three (severin, fragmin, adseverin/scinderin) (Ampe et al, 1987; Andr et al, 1988; Nakamura et al,1994) , homologous domains.  Class II capping proteins in the gelsolin group consist of three domains.  Given the domain structure of gelsolin, hypothesis have naturally been forwarded suggesting that the whole group arose by two major events.  First, a 15,000 proto-actin binding protein became triplicated to form some members such as severin, and this gene then was subsequently duplicated to form gelsolin.  It is additionally supposed that villin arose from gelsolin, by the addition of a "head piece" (Yin, 1988) endowing this group with bundling activity (Friederich et al, 1989; Finidori et al,1992).  The hypothetical 15,000 Da proto- ABP, has not yet been discovered in nature in as much as no protein of this size with recognisable sequence to the gelsolin fold has been found.  However, although the ADF/cofilin group share no recognisable sequence homology, they do share a remarkable similarity in tertiary structure (Hatanaka et al, 1996), and a related group of ABPs, the twinfilins (Goode et al, 1998), consisting of two ADF/cofilin motifs have been discovered, in support of the general duplication hypothesis.  Again in favour of the hypothesis is the finding that the triple-domain proteins severin and fragmin are abundant in slime moulds and it seemed at first that the hexuple forms were only found in metazoans, since then villin-like proteins with six domains have been reported in Dictyostelium (Hofman et al, 1993) and possibly primitive eukaryote, Entamoeba (Ebert, 1993; 2000) spoiling this attractively simple hypothesis. 

The Gelsolin family structural repeat.

The segmental structure of the gelsolin family is apparent not only from the primary structure (Way & Weeds, 1988; Finidori et al, 1992) but from the inter-segmental location of proteolysis site (Kwiatkowski et al, 1985; Bryan & Hwo, 1986; Kwiatkowski et al, 1989) by differential stability and solubility of recombinantly expressed domains (Way et al, 1989; 1990; Pope et al, 1994). Each domain is between 125 and 150 residues.  The 3D structure of gelsolin domain 1 (McLaughlin et al, 1994).

Gelsolin Segment 1

Gelsolin segment 1 (G1) is the best characterised of all segments of the gelsolin family.  It was originally described as an N-terminal 17kDa chymotryptic fragment (CT14N) (Yin et al, 1988) that retained some actin binding functions. G1 binds actin monomer in a calcium insensitive manner, although a calcium is "trapped" between G1 and actin. G1 with an additional 10 amino-acids from the start of G2 is sufficiently for a weak severing activity.  This activity is about 100 times less than the whole protein.

Gelsolin Segment 2

(G2) contains a second PIP2 binding domain, and an F-actin actin binding site. The actin side-binding domain also has actin filament capping activity (Sun et al, 1994). The actin binding site is between 150-173 (Sun et al, 1994). The solution structure of segment 2 of severin has been deduced (Schuchel et al, 1994).  G2 also binds tropomyosin (Maciver et al, 2000) in a Ca2+ and pH sensitive manner reminiscent of the interaction.

Gelsolin Segment 3

(G3) No known function other than that of a spacer.

Gelsolin Segment 4

Sequence comparisons reveals G4 to be most similar to G1 and this is borne out by a comparison of the domain structures (Burtnick et al, 1997). G4 also binds to G-actin in a similar manner as G1 (Pope et al, 1996 ).

Gelsolin Segment 5

Gelsolin Segment 6

 

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Actin Binding Activity of the Gelsolin Family

Monomeric Actin Binding.  In the presence of Ca2+, gelsolin binds two actin monomers (Yin & Stossel, 1980; Bryan & Kurth, 1984).

Filament Binding. In addition to the two monomeric actin binding sites discussed above, gelsolin binds actin filaments by a third actin binding site.  Actually, this third site binds very weakly to actin monomers, but does not compete with G1 or G4-6 for binding indicating that the F-binding site binds at a different site on actin (Pope et al, 1990).

Capping activity.  Gelsolin binds two actin monomers to form a nucleus for actin polymerization and caps the barbed end of actin filaments. Chemical crosslinking studies (Doi, 1992) indicate that gelsolin indeed binds two actins diagonally apposite monomers, rather than the two longitudinal monomers supporting this notion.  Both G-actin binding sites (in G1 and G4) bind the same domain on actin (Pope et al, 1990).

Severing activity.  Severing of actin filaments requires G1 plus 10 residues of G2 ().  The severing activity of this fragment is about 100 times less than the whole protein, however with the F-actin binding domain present in G2, G1-2 (Way et al, 1992), is fully activity.  Severing of actin filaments by gelsolin is inhibited by phalloidin

Nucleation of actin polymerization.  Actin polymerizes from actin monomers, to form microfilaments when several criteria are satisfied (Pollard & Cooper, 1995; Sheterline & Sparrow, 1994).  The monomeric actin concentration must exceed the "critical concentration" (~0.1mm for ATP-bound actin in the absence of actin binding proteins, and in the presence of 1mM magnesium and salts greater than 50mM). These conditions exist in most if not all eukaryotic, yet approximately 50% of the actin in cells is monomeric.  A variety of actin binding proteins (such as the thymosins, ADF/cofilin and profilin) are thought to be responsible for the sequestration of this monomeric actin pool by preventing polymerization.  This "extra" intracellular actin can be polymerised upon supply of nucleation sites at.  Gelsolin has been known for some time to bind the barbed end of actin filaments (Wilkin et al, 1983) and to nucleate the polymerization of actin (Tellam & Frieden 1982).

 

Gelsolin vs Villin

The main difference between gelsolin and villin is the additional actin binding domain at the COOH terminus of villin; the inaptly named "head piece".  The head piece is reponsible for villins bundling activity (Glenney & Weber, 1981; Friederich et al, 1989), and is strongly homologous with a region of dematin (band 4.9) an actin bundling protein (Rana et al, 1993), Dictyostelium "proto-villin" (Hofmann et al, 1993).  The villin head piece binds actin on sub-domain 1, since it competes for binding with ADF (Pope et al, 1993) (which is presumed to bind primarily to sub-domain 1 and the lower-rear surface of sub-domain 2, see ADF/cofilin).  The head piece however, is not the only difference between gelsolin and villin as the placement of villin head piece in the analogous place in gelsolin does not produce microvilli as villin does when transfected into cells lacking them, but instead disrupts stress fibres (Finidori et al, 1992; Friedrich et al, 1992).  

Tissue distribution of the Gelsolins

There would appear to be a conserved tendency for gelsolins to be encoded by a single gene and to encode both a cytoplasmic and a serum form. This is true of the single human gelsolin gene (Kwaiatkowski et al, 1986) encodes both cytoplasmic gelsolin variant and the secreted form, chromosome 9 (Kwiatkowski et al, 1988b &c) cand the rat gelsolin gene (Vouyioklis & Brophy, 1997).  Even in Drosophila a form is secreted into the haemolymph (Stella et al, 1994). Muscle tissue is the major source of serum gelsolin (Nodes et al, 1987; Kwiatkowski et al, 1988a).  

Cellular localisation of the Gelsolins.

Gelsolin has been reported to be localized generally to actin rich structures (Yin et al, 1981) while others have concluded that gelsolin is diffusely distributed in platelets, white blood cells (Chaponnier et al, 1985) and cultured lymphoid cells (Thorstensson et al, 1982).  Ovary (Teubner et al, 1993 & 1994). Gelsolin has been localised in regions of cell-substratum contact or attachment in Rous sarcoma virus-transformed rat cells (Wang et al, 1984).  However, immunolocalization of gelsolin has been hampered by the fact that gelsolin is present at high concentration (0.2mgs/ml) (Kwiatkowski et al, 1988b) in vertebrate serum, contaminating many reagents used in immunolocalization studies.  Many studies have therefore erroneously concluded that gelsolin is localized along filaments in permeablized cells of a variety of types (Carron et al, 1986).  With this caveat in mind, more recent work has concluded that gelsolin is localized at the cell periphery in platelets (Carron et al, 1986).  Other studies since the report of Carron and coworker's work, designed to eliminate the risk of xenogenic gelsolin still insist that gelsolin is located along stress fibres in fibroblasts (Kanno & Sasaki, 1989; Dissman & Hinssen, 1994) and in the I-Z-I region in muscle cells (Dissman & Hinssen, 1994).  Immunogold ultra-structural electron microscopy (Hartwig et al, 1989), has revealed that gelsolin is associated with actin filaments and cell membranes of macrophages and platelets, presumably in association with polyphosphoinositides.  In neuronal cells gelsolin has been localized to the growth cone (Tanaka et al, 1993) and to the (Tanaka & Sobue,1994)

The location of other members of the gelsolin family have been less controversially determined.  Severin has been found to be concentrated at the leading edge of Dictyostelium amoebae (Brock & Pardee, 1985).  Adseverin/scinderin become localised to the cortex of secretory cells where they apparently remove actin around the vesicles to allow them to dock and fuse with the plasma-membrane (see Adseverin/Scinderin). Gcap is present in both the cytoplasm and the nucleus (Onoda & Yin, 1993; Prendergast & Ziff, 1991). Nuclear targeting of the protein is apparently stimulated by serine-threonine phosphorylation (Onoda & Yin, 1993).  Villin has also been localised to the microvillus in a number of studies (Matsudaira, 1992). Fragmin has been localised within the plasmodium of Physarum (Osborn et al, 1983; T'Jampens et al, 1997)

Gelsolins and Cytokinesis?  Many ABPs are known to be concentrated with actin in the cleavage furrow at cytokinesis and since the furrow depolymerizes as it contracts and gelsolins are proteins that depolymerize actin filaments it may be expected that gelsolin is a component of the cleavage furrow.  However, evidence for this has been slow n coming forward.  In contrast cofilin (another actin depolymerising protein) is known to concentrate in the furrow.  

Post Translational Modification of Gelsolins.

Phosphorylation  Gelsolin itself is not thought to be phosphorylated under "normal" conditions (Wang et al, 1984; Onoda & Yin, 1993), however it has been reported to be phosphorylated  by PP60c-src in the presence of PIP2 (De Corte et al, 1997). 

 

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Gelsolins and cancer

Gelsolin levels have often been discovered to be lowered in oncogenic transformations (Vandekerckhove et al, 1990; Asch et al, 1996)  A mutation in gelsolin is responsible for the transformation.  The mechanism by which gelsolin is down-regulated may be through epigenetic changes in chromatin structure through histone acetylation (Mielnicki et al, 1999). The role (if any) between oncogenic transformation and gelsolin may be connected to the role that gelsolin seems to have in apoptosis (see below).  Villin is used as a marker for bowel ( ) and kidney cancers (Grone et al, 1986).

 

Gelsolins in other diseases

FAF, Lewy bodies,

Gelsolin and Cystic Fibrosis
Gelsolin Related Proteins
Adeseverin/Scinderin

Although Adseverin (also known as scinderin) appears to be a smaller protein on SDS-PAGE than gelsolin, it shares the same overall domain structure and is approximately the same size.  Adseverin is expressed in a wide variety of tissues and is especially abundant in brain.  It appears to have a specific role in regulated secretion.  (See Adeseverin/Scinderin pages).

 

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Flightless-I

The flightless-I gene is required for cellularisation in the early embryo of Drosophila melanogaster (Campbell et al, 1993).  

 

Gelsolin as a tool

References:-

Allen, P. G. & Janmey, P. A. (1994) Gelsolin displaces phalloidin from actin filaments., J. Biol. Chem. 269, 32916-32923.

Ampe, C. & Vandekerckhove, J. (1987) The F-actin capping proteins of Physarum polycephalum: cap42(a) is very similar, if not identical, to fragmin and is structually and functionally very homologous to gelsolin; cap42(b) is Physarum actin., EMBO J. 6, 4149-4157.

André, E., Lottspeich, F., Schleicher, M. & Noegel, A. (1988) Severin, gelsolin, and villin share a homologous sequence in regions presumed to contain F-actin severing domains., J. Biol. Chem. 263, 722-728.

Ankenbauer, T., Kleinschmidt, J. A., Vandekerckhove, J. & Franke, W. W. (1988) Proteins regulating actin assembly in oogenesis and early embryogenesis of Xenopus laevis: gelsolin is the major cytoplasmic actin-binding protein., J. Cell Biol. 107, 1489-1498.

Arora, P. D. & McCulloch, C. (1996) Relationship of actin-binding and severing to gelsolin expression in fibroblast migration, Journal Of Dental Research. 75, 2754-2754.

Arora, P. D. & McCulloch, C. (1996) Dependence of fibroblast migration on actin severing activity of gelsolin, Journal Of Biological Chemistry. 271, 20516-20523.

Arora, P. D., Janmey, P. A. & McCulloch, C. A. G. (1999) A role for gelsolin in stress fiber-dependent cell contraction., Exp.Cell Res. 250, 155-157.

Asch, H. L., Head, K., Dong, Y., Natoli, F., Winston, J. S., Connolly, J. L. & Asch, B. B. (1996) Widespread loss of gelsolin expression in breast cancers of humans, mice, and rats., Cancer Res. 56, 4841-4846.

Allen, P. G., Laham, L. E., Way, M. & Janmey, P. A. (1996) Binding of phosphate, aluminium fluoride, or beryllium fluoride to F- actin inhibits severing by gelsolin, J.Biol.Chem. 271, 4665-4670.

Allen, P. G. (1997) Functional consequences of disulfide bond formation in gelsolin., FEBS letters. 401, 89-94.

Bearer, E. L., Prakash, J. M., Manchester, R. D. & Allen, P. G. (2000) VASP protects actin filaments from gelsolin: An in vitro study with implications for platelet actin reorganizations., Cell Motility Cytoskeleton. 47, 351-364.

Banyard, M. R. C., Medveczyk, C. J. & Tellam, R. L. (1990) Microfilament organization correlates with increased cellular content of gelsolin., Exptl. Cell Res. 187, 180-183.

Baldassare, J. J., Henderson, P. A., Tarver, A. & Fisher, G. J. (1997) Thrombin activation of human platelets dissociates a complex containing gelsolin and actin from phosphatidylinositide-specific phospholipase Cg1., Biochem. J. 324, 283-287.

Barkalow, K., Witke, W., Kwiatkowski, D. J. & Hartwig, J. H. (1996) Coordinated regulation of platelet actin filament barbed ends by gelsolin and capping protein, Journal Of Cell Biology. 134, 389-399.

Bearer, E. L. (1991) Direct observation of actin filament severing by gelsolin and binding by gCap39 and CapZ, J. Cell Biol. 115, 1629-1638.

Bock, D., Hinssen, H. & D'Haese, J. (1994) A gelsolin-related actin-severing protein with fully reversible actin-binding properties form the tail muscle of crayfish, Astacus leptodactylus., Eur. J. Biochem. 225, 727-735.

Borovikov, Y. S., Norman, J. V., Price, L. S., Weeds, A. G. & Koffer, A. (1995) Secretion from permeabilised mast cells is enhanced by addition of gelsolin: contrasting effects of endogenous gelsolin., J. Cell Sci. 108, 657-666.

Bryan, J. & Kurth, M. C. (1984) Actin-gelsolin interactions. Evidence for two actin-binding sites, J. Biol. Chem. 259, 7480-7487.

Bryan, J. (1988) Gelsolin has three actin-binding sites., J. Cell Biol. 106, 1553-1562.

Bryan, J. (1992) Isolation and characterization of platelet gelsolin, Methods In Enzymology. 215, 88-99.

Bryan, J. & Coluccio, L. M. (1985) Kinetic analysis of F-actin depolymerization in the presence of platelet gelsolin and gelsolin-actin complexes, J. Cell Biol. 101, 1236-1244.

Burtnick, L. D., Robinson, R. C. & Koepf, E. K. (1996) The structure of horse plasma gelsolin to 2.5 angstrom, Biophysical Journal. 70, SUA12-SUA12.

Burtnick, L. D., Koepf, E. K., Grimes, J., Jones, E. Y., Stuart, D. I., McLaughlin, P. J. & Robinson, R. C. (1997) The crystal structure of plasma gelsolin: Implications for actin severing, capping and nucleation., Cell. 90, 661-670.

Campbell, H. D., Schimansky, T., C.Claudianos, Ozsarac, N., Kasprzak, A. B., Cotsell, J. N., Young, I. G., Couet, H. G. d. & Miklos, G. L. G. (1993) The Drosophila melanogaster flightless-I gene involved in gastrulation and muscle degeneration encodes gelsolin-like and leucine-rich repeat domains and is conserved in Caenorhabditis elegans and humans, Proc. Natl. Acad. Sci. 90, 11386-11390.

Campbell, H. D., Fountain, S., Young, I. G., Claudianos, C., Hoheisel, J. D., Chen, K.-S. & Lupski, J. R. (1997) Genomic structure, evolution, and expression of human FLII, a gelsolin and leucine-rich-repeat family member: overlap with LLGL, Genomics. 42, 46-54

Carron, C.P., Hwo, S., Dingus, J., Benson, D.M., Meza, I., Bryan, J. (1986). A re-evaluation of cytoplasmic gelsolin localization. J.Cell Biol. 102, 237-245.

Carson, M. R., Shasby, S. S., Lind, S. E. & Shasby, D. M. (1992) Histamine, actin-gelsolin binding, and polyphosphoinositides in human umbilical vein endothelial-cells, Amer. J. Physiology. 263, 664-669.

Chapelle, A. d. l., Tolvanen, R., Boysen, G., Santavy, J., Bleeker-Wagemakers, L., Maury, C. P. J. & Kere, J. (1992) Gelsolin-derived familial amyloidosis caused by asparagine or tyrosine substitution for aspartic acid at residue 187, Nature genetics. 2, 157-160.

Chaponnier, C., Janmey, P. A. & Yin, H. L. (1986) The actin filament-severing domain of plasma gelsolin., J. Cell Biol. 103, 1473-1481.

Chaponnier, C. & Gabbiani, G. (1989) Gelsolin modulation in epithelial and stromal cells of mammary-carcinoma, American Journal Of Pathology. 134, 597-603.

Chauhan, V. P. S., Ray, I., Chauhan, A. & Wisniewski, H. M. (1999) Binding of gelsolin, a secretory protein, to amyloid b-protein., B.B.R.C. 258, 241-246.

Chauhan, V., Singh, S., Murakami, N. & Chauhan, A. (1996) Profilin and gelsolin stimulate phosphatidylinositol 3-kinase activity, Faseb Journal. 10, L 47-L 47.

Chen, P., Murphy-Ullrich, J. E. & Wells, A. (1996) A role for gelsolin in actuating epidermal growth factor receptor- mediated cell motility, Journal Of Cell Biology. 134, 689-698.

Chellaiah, M. & Hruska, K. (1996) Osteopontin stimulates gelsolin-associated phosphoinositide levels and phosphatidylinositol trisphosphate-hydroxyl kinase, Mol.Biol.Cell. 7, 743-753.

Cortese, J. D. & Freiden, C. (1990) Effect of filamin and controlled linear shear on the microheterogeneity of F-actin/gelsolin gels., Cell Motility Cytoskeleton. 17, 236-249.

Cooper, J. A., Bryan, J., Schwab III, B., Frieden, C., Loftus, D. J. & Elson, E. L. (1987) Microinjection of gelsolin into living cells., J.Cell Biol. 104, 491-501.

Coué, M. & Korn, E. D. (1985) Interaction of plasma gelsolin with G-actin and F-actin in the presence and absence of calcium ions., J. Biol. Chem. 260, 15033-15041.

Coué, M. & Korn, E. D. (1986) ATP hydrolysis by the gelsolin-actin complex and at the pointed ends of gelsolin-capped filaments., J.Biol. Chem. 261, 1588-1593.

Coué, M. & Korn, E. D. (1986) Interaction of plasma gelsolin with ADP-actin, J. Biol. Chem. 261, 3628-3631.

Cunningham, C. C., Stossel, T. P. & Kwiatkowski, D. J. (1991) Enhanced motility in NIH 3T3 fibroblasts that overexpress gelsolin, Science. 251, 1233-1236.

Dabrowska, R., Hinssen, H., Galazkiewicz, B. & Nowak, E. (1996) Modulation of gelsolin-induced actin-filament severing by caldesmon and tropomyosin and the effect of these proteins on the actin activation of myosin mg2+-atpase activity, Biochemical Journal. 315, 753-759.

Dadabay, C. Y., Patton, E., Cooper, J. A. & Pike, L. J. (1991) Lack of Correlation between Changes in Polyphosphoinositide Levels and Actin/Gelsolin Complexes in A431 Cells Treated with Epidermal Growth Factor, Journal of Cell Biology. 112, 1151-1156.

Deaton, J. D., Guerrero, T. & Howard, T. H. (1992) Role of gelsolin interaction with actin in regulation and creation of actin nuclei in chemotactic peptide activated polymorphonuclear neutrophils, Molecular Biology of the Cell. 3, 1427-1435.

Debleecker, J. L. & Engel, A. G. (1994) Myopathy with desmin excess .2. ectopic overexpression of multiple proteins (including dystrophin, gelsolin, ncam, and serin protease inhibitors) and congophilia., Neurology. 44, 346-347.

De Corte, V., Gettemans, J. & Vandekerckhove, J. (1997) Phosphatidylinositol 4,5-bisphosphate specifically stimulates PP60c-src catalyzed phosphorylation of gelsolin and related actin-binding proteins., FEBS letters. 401, 191-196.

DelaChapelle, A., Tolvanen, R., Boysen, G., Santavy, J., Bleekerwagemakers, L., Maury, C. P. J. & Kere, J. (1992) Gelsolin-derived familial amyloidosis caused by asparagine or tyrosine substitution for aspartic-acid at residue 187, Nature (Genetics). 2, 157-160.

Dieffenbach, C. W., SenGupta, D. N., Krause, D., Sawzak, D. & Silverman, R. H. (1989) Cloning of murine gelsolin and its regulation during differentiation of embryonal carcinoma cells., J. Biol. Chem. 264, 13281-13288.

Dinubile, M. J. & Southwick, F. S. (1985) Effects of macrophage profilin on actin in the presence and absence of acumentin and gelsolin, Journal Of Biological Chemistry. 260, 7402-7409.

Dissmann, E., Gimona, M. & Hinssen, H. (1993) Immunocytochemical localization of gelsolin in muscle and nonmuscle cells, Journal Of Muscle Research And Cell Motility. 14, 275.

Dissmann, E. & Hinssen, H. (1994) Immunocytochemical localization of gelsolin in fibroblasts, myogenic cells, and isolated myofibrils, European Journal Of Cell Biology. 63, 336-344.

Ditsch, A. & Wegner, A. (1994) Nucleation of actin polymerization by gelsolin, Eur. J. Biochem. 224, 223-227.

Ditsch, A. & Wegner, A. (1995) Two low-affinity Ca2+ binding sites that regulate association with actin, Eur. J. Biochem. 229, 512-516.

Doi, Y., Higashida, M. & Kido, S. (1987) Plasma gelsolin binding sites on the actin sequence., Eur. J. Biochem. 164, 89-94.

Doi, Y., Kim, F. & Kido, S. (1990) Weak binding of divalent cations to plasma gelsolin, Biochemistry. 29, 1392-1397.

Doi, Y., Banba, M. & Vertut-Doi, A. (1991) Cysteine-374 of actin resides at the gelsolin contact site in the EGTA-resistant actin-gelsolin complex, Biochemistry. 30, 5769-5777.

Doi, Y., Hashimoto, T., Yamaguchi, H. & Vertut-Doi, A. (1991) Modification of gelsolin with 4-fluor-7-nitro-2-oxa-1,3-diazole, Eur. J. Biochem. 199, 277-283.

Doi, Y. (1992) Interaction of gelsolin with covalently cross-linked actin dimer, Biochemistry. 31, 10061-10069.

Doi, Y., Kanatani, Y. & Kim, F. (1992) The amino-terminal fragment of gelsolin is cross-linked to Cys-374 of actin in the EGTA-reeistant actin-gelsolin complex, FEBS Lett, 99-102.

D'Haese, J., Rutschmann, M., Dahlmann, B. & Hinssen, H. (1987) Activity of a gelsolin-like actin modulator in rat skeletal muscle under protein catabolic conditions., Biochem. J. 248, 397-402.

Ebert, F., Buss, H., Horstmann, R.D. & Tannich, E. (1993). Putative actin filament-severing protein of the protozoan parasite Entamoeba histolytica contains "headpiece"-like domain and unusual N-terminal extension. Mol.Biol.Cell. 4, 19a.

Ebert, F., Guillen, N., Leippe, M. & Tannich, E. (2000) Molecular cloning and cellular localization of an unusual bipartite Entamoeba histolytica polypeptide with similarity to actin binding proteins., Mol.Biochem.Parasitol. 111, 459-464.

Endres, M., Fink, K., Zhu, J., Stagliano, N. E., Bondada, V., Geddes, J. W., Azuma, T., Matteson, M. P., Kwiatkowski, D. J. & Moskowitz, M. A. (1998) Neuroprotective effects of gelsolin during murine stroke, J.Clin.Invest. 103, 347-354.

Feinberg, J., Capony, J. P., Benyamin, Y. & Roustan, C. (1993) Definition of the EGTA-independent interface involved in the serum gelsolin actin complex, Biochemical Journal. 293, 813-817.

Feinberg, J., Mery, J., Heitz, F., Benyamin, Y. & Roustan, C. (1996) Correlations between biological-activity and structural-properties for 2 short homologous sequences in thymosin beta-4 and gelsolin, International Journal Of Peptide And Protein Research. 47, 62-69.

Feinberg, J., Benyamin, Y. & Roustan, C. (1995) Definition of an interface implicated in gelsolin binding to the sites of actin filaments, Biochem. Biophys. Res. Comm. 209, 426-432.

Feinberg, J., Lebart, M.-C., Benyamin, Y. & Roustan, C. (1997) Localization of a calcium sensitive binding site for gelsolin on actin subdomain I: Implication for severing process, Biochem.Biophys.Res.Comm. 233, 61-65.

Finidori, J., Friederich, E., Kwiatkowski, D. J. & Louvard, D. (1992) In vivo analysis of functional domains from villin and gelsolin, J Cell Biol. 116, 1145--1155.

Flanagan, L. A., Cunningham, C. C., Chen, J., Prestwich, G. D., Kosik, K. S. & Janmey, P. A. (1997) The structure of divalent cation-induced aggregates of PIP2 and their alteration by gelsolin and tau, Biophys.J. 73, 1440-1447.

Fong, K. S. K. & de Couet, H. G. (1999) Novel proteins interacting with the leucine-rich repeat domain of human flightless-1 identified by the yeast two-hybrid system., Genomics. 58, 146-157.

Fujita, H., Laham, L. E., Janmey, P. A., Kwiatkowski, D. J., Stossel, T. P., Banno, Y., nozawa, Y., Mullauer, L., Ishizaki, A. & Kuzumaki, N. (1995) Functions of [his321] gelsolin isolated from a flat revertant of ras- transformed cells, European Journal Of Biochemistry. 229, 615-620.

Fujita, H., Allen, P. G., Janmey, P. A., Azuma, T., Kwiatkowski, D. J., Stossel, T. P., Furu-uchi, K. & Kuzumaki, N. (1997) Characterization of gelsolin truncates that inhibit actin polymerization by severing activity of gelsolin and cofilin, Eur.J.Biochem. 248, 834-839.

Funatsu, T., Higuchi, H. & Ishiwata, S. (1990) Elastic filaments in skeletal muscle revealed by selective removal of thin filaments with plasma gelsolin, J. Cell Biol. 110, 53-62.

Funatsu, N., Kumanogoh, H., Sokawa, Y. & Maekawa, S. (2000) Identification of gelsolin as an actin regulatory component in a Triton insoluble low density fraction (raft) of newborn bovine brain., Neuroscience Research. 36, 311-317.

Gershman, L. C., Selden, L. A., Kinosian, H. J. & Estes, J. E. (1993) Evidence that gelsolin severing activity is greater with Mg-actin than with Ca-actin, Biophysical Journal. 64, 148.

Geng, Y.-J., Azuma, T., Tang, J. T., Hartwig, J. H., Muszynski, M., Wu, Q., Libby, P. & Kwiatkowski, D. J. (1998) Caspase-3-induced gelsolin fragmentation contributes to actin cytoskeletal collapse, nucleolysis, and apoptosis of vascular smooth muscle cells exposed to proiflammatory cytokines, Eur.J.Cell Biol. 77, 294-302.

Giebing, T., Langer, M., Serwe, C., Digregorio, A., Dilauro, R. & Dhaese, J. (1996) Gelsolin-like proteins from tunicates - analytical approach at both protein and DNA level, Journal Of Muscle Research And Cell Motility. 17, 111-111.

Gimona, M., Lando, Z., Dolginov, Y., Vandekeckhove, J., Kobayashi, R., Sobieszek, A. & Helfman, D. M. (1997) Ca2+-dependent interaction of S100A2 with muscle and non-muscle tropomyosins, J.Cell Sci. 110, 611-621.

Granzier, H. L. M. & Wang, K. (1993) Interplay between passive tension and strong and weak binding cross-bridges in insect indirect flight muscle: a functional dissection by gelsolin-mediated thin filament removal, Journal of General Physiology. 101, 235-270.

Gremm, D. & Wegner, A. (1999) Co-operative binding of Ca2+ ions to the regulatory binding sites of gelsolin., Eur.J.Biochem. 262, 330-334.

Gremm, D. & Wegner, A. (2000) Gelsolin as a calcium-regulated actin filament-capping protein., Eur.J.Biochem. 267, 4339-4345.

Goverman, J., Schick, L. A. & Newman, J. (1996) The bundling of actin with polyethylene-glycol 8000 in the presence and absence of gelsolin, Biophysical Journal. 71, 1485-1492.

Goetzl, E. J., Lee, H., Azuma, T., Stossel, T. P., Turck, C. W. & Karliner, J. S. (2000) Gelsolin binding and cellular presentation of lysophosphatidic acid., J.Biol.Chem. 275, 14573-14578.

Gonsior, S. & Hinssen, H. (1995) Exogenous gelsolin binds to sarcomeric thin filaments without severing, Cell Mot. Cytoskeleton. 31, 196-206.

Goode, B. L., Drubin, D. G. & Lappalainen, P. (1998) Regulation of the cortical actin cytoskeleton in budding yeast by twinfilin, a ubiquitous actin monomer sequestering protein., J.Cell Biol. 142, 723-733.

Goshima, M., Kariya, K.-i., Yamawaki-Kataoka, Y., Okada, T., Shibatohge, M., Shima, F., Fujimoto, E. & Kataoka, T. (1999) Characterization of a novel Ras-binding protein Ce-FLI-1 comprising leucine-rich repeats and gelsolin-like domains., BBRC. 257, 111-116.

Grone, H.J., Weber, K., Helmchen, U., & Osborn, M. (1986). Villin- a marker of brush border differentiation and cellular origins in human renal cell carcinoma. Am.J.Pathol. 124, 294-302.

Haltia, M., Ghiso, J., Prelli, F., Gallo, G., Kiuru, S., Somer, H., Palo, J. & Frangione, B. (1990) Amyloid in familial amyloidosis, finnish type, is antigenically and structurally related to gelsolin, Am J Path. 136, 1223-1228.

Harris, H.E., Bamburg, J.R. & Weeds, A.G. (1980). Actin filament disassembly in blood plasma. FEBS lett. 123, 49-53.

Harris, H. E. (1985) Lack of nucleotide exchange on the binding of G-actin-ATP to plasma gelsolin, FEBS Lett. 190, 81-83.

Harris, H. E. (1988) The binary complex of pig plasma gelsolin with Mg2+-G- actin in ATP and ADP, FEBS Lett. 233, 359-362.

Hartwig, J. H., Chambers, K. A. & Stossel., T. P. (1989) Association of gelsolin with actin and cell membranes of macrophages and platelets., J Cell Biol. 108, 467-479.

Haskell, J., Newman, J., Selden, L. A., Gershman, L. C. & Estes, J. E. (1994) Viscoelastic parameters for gelsolin length regulated actin-filaments, Biophysical Journal. 66, 196.

Hatanaka, H., Ogura, K., Moriyama, M., Ichikawa, S., Yahara, I. & Inagaki, F. (1996) Tertiary structure of destrin and structural similarity between two actin-regulating protein families, Cell. 85, 1047-1055.

Heintzelman, M. B., Frankel, S. A., Artavanis-Tsakonas, S. & Mooseker, M. S. (1993) Cloning of a secretory gelsolin from Drosophila melanogaster., J. Mol. Biol. 230, 709-716.

Hellweg, T., Hinssen, H. & Eimer, W. (1993) Dynamic light-scattering study on the 2 proteolytic fragments of gelsolin, Journal Of Muscle Research And Cell Motility. 14, 275-276.

Hellweg, T., Hinssen, H. & Eimer, W. (1993) The calcium-induced conformational change of gelsolin is located in the carboxyl-terminal half of the molecule, Biophys. J. 65, 799-805.

Hesterkamp, T., Weeds, A. G. & Mannherz, H. G. (1993) The actin monomers in the ternary gelsolin:2 actin complex are in antiparallel orientation., Eur. J. Biochem. 218, 507-513.

 Hirsch, M. S. & Svlboda, K. (1994) Intracellular-localization of vinculin and gelsolin in embryonic avian corneal epithelia, Investigative Ophthalmology & Visual Science. 35, 1940.

Hiyoshi, M., Nakao, Y. & Tatsumi, N. (1994) Comparison of 2 monoclonal-antibodies, h6b11 and gs2c4, against human plasma gelsolin, Biochemistry And Molecular Biology International. 32, 755-762.

Huckriede, A., Hinssen, H., Jockusch, B. M. & Lazarides, E. (1988) Gelsolin sensitivity of microfilaments as a marker for muscle differentiation, Eur.J.Cell Biol. 46, 506-512.

Huckriede, A., Fuchtbauer, A., Hinssen, H., Chaponnier, C., A.Weeds & Jockusch, B. (1990) Differential effects of gelsolins in tissue culture cells., Cell Motility and the Cytoskeleton 16, 229-238 (1990). 16, 229-238.

Isaacson, R. L., Weeds, A. G. & Fersht, A. R. (1999) Equilibria and kinetics of folding of gelsolin domain 2 and mutants involved in familial amyloidosis-Finnish type., PNAS. 96, 11247-11252.

Ishikawa, R., Yamashiro, S. & Matsumura, F. (1989) Differential modulation of actin-severing activity of gelsolin by multiple isoforms of cultured rat cell tropomyosin., J. Biol. Chem. 264, 7490-7497.

Ishikawa, R., Yamashiro, S. & Matsumura, F. (1989) Annealing of gelsolin-severed actin fragments by tropomyosin in the presence of calcium, J. Biol. Chem. 264, 16764-16770.

Ishizaki, A., Fujita, H. & Kuzumaki, N. (1995) Growth-inhibitory functions of a mutated gelsolin (His321) in NIH/3T3 mouse fibroblasts, Exptl Cell Res. 217, 448-452.

Janmey, P. A., Chaponnier, C., Lind, S. E., Zaner, K. S., Stossel, T. P. & Yin, H. L. (1985) Interactions of gelsolin and gelsolin-actin complexes with actin. Effects of calcium on actin nucleation, filament severing and end blocking., Biochemstry. 24, 3714-3723.

Janmey, P. A., Stossel, T. P. & Lind, S. E. (1986) Sequential binding of actin monomers to plasma gelsolin and its inhibition by vitamin D-binding protein, Biochem. Biophys. Res. Comm. 136, 72-79.

Janmey, P. A. & Stossel, T. P. (1986) Kinetics of actin monomer exchange at the slow growing ends of actin filaments and their relationship to the elongation of filaments shortened by gelsolin, J. Muscle Res & Cell Motility. 7, 446-454.

 Janmey, P. A. & Stossel, T. P. (1987) Modulation of gelsolin function by phosphatidylinositol 4,5-bisphosphate, Nature. 325, 362-364.

Janmey, P. A., Iida, K., Yin, H. L. & Stossel, T. P. (1987) Polyphosphoinositide micelles and polyphosphoinoositide-containing vesicles dissociate endogenous gelsolin-actin complexes and promote actin assembly from the fast-growing end of actin filaments blocked by gelsolin, J. Biol. Chem. 262, 12228-12236.

Janmey, P. A. & Matsudaira, P. T. (1988) Functional comparison of villin and gelsolin, J. Biol. Chem. 263, 16738-16743.

Janmey, P. A., Hvidt, S., Peetermans, J., Lamb, J., Ferry, J. D. & Stossel, T. P. (1988) Viscoelasticity of F-actin and F-actin/gelsolin complexes, Biochemistry. 27, 8218-8227.

Janmey, P. A. & Stossel, T. P. (1989) Gelsolin-polyphosphoinositide interaction, J. Biol. chem. 264, 4825-4831.

Janmey, P. A., Lamb, J., Allen, P. G. & Matsudaira, P. T. (1992) Phosphoinositide-binding peptides derived from the sequences of gelsolin and villin, Journal Of Biological Chemistry. 267, 11818-11823.

Just, I., Wille, M., Chaponnier, C. & Aktories, K. (1993) Gelsolin-actin complex is target for ADP-ribosylation by Clostridium-botulinum c2 toxin in intact human neutrophils, European Journal Of Pharmacology-molecular Pharmacology Section. 246, 293-297.

Kambe, H., Ito, H., Kimura, Y., Okochi, T., Yamamoto, H., Hashimoto, T. & Tagawa, K. (1992) Human plasma gelsolin reversibly binds Mg-ATP in Calcium-sensitive manner., J. Biochem. 111, 722-725.

Kangas, H., Paunio, T., Kalkkinen, N., Jalanko, A. & Peltonen, L. (1996) In-vitro expression analysis shows that the secretory form of gelsolin is the sole source of amyloid in gelsolin-related amyloidosis, Human Molecular Genetics. 5, 1237-1243.

Kangas, H., Ulmanen, I., Paunio, T., Kwiatkowski, D. J., Lehtovitro, M., Jalanko, A. & Peltonen, L. (1999) Functional consequences of amyloidosis mutation for gelsolin polyproline-analysis of gelsolin-actin interaction and gelsolin processing in gelsolin knock-out fibroblasts., FEBS letters. 454, 233-239.

Khaitlina, S. & Hinssen, H. (1997) Conformational changes in actin induced by its interaction with gelsolin, Biophys.J. 73, 929-937.

Kinosian, H. J., Newman, J., Lincoln, B., Selden, L. A., Gershman, L. C. & Estes, J. E. (1998) Ca2+ regulation of gelsolin activity: Binding and severing of F-actin, Biophys. J. 75, 3101-3109.

Kinosian, H. J., Selden, L. A., Estes, J. E. & Gershman, L. C. (1996) Kinetics of gelsolin interaction with phalloidin-stabilized F-actin. Rate constants for binding and severing., Biochemistry. 35, 16550-16556.

Koepf, E. K. & Burtnick, L. D. (1992) Interaction of plasma gelsolin with tropomyosin, FEBS. 309, 56-58.

Koepf, E. K. & Burtnick, L. D. (1993) Thermal-stability of FITC-labeled plasma gelsolin, Faseb Journal. 7, 1287.

Koepf, E. K. & Burtnick, L. D. (1993) Horse plasma gelsolin labelled with fluorescein isothiocyanate responds to calcium and actin, Eur. J. Biochem. 212, 713-718.

Koepf, E. K. & Burtnick, L. D. (1996) Multiple pathways for denaturation of horse plasma gelsolin, Biochemistry And Cell Biology Biochimie Et Biologie Cellulaire. 74, 101-107.

Koepf, E. K., Hewitt, J., Vo, H., Macgillivray, R. T. A. & Burtnick, L. D. (1998) Equus caballus gelsolin. cDNA sequence and protein structural implications, Eur.J.Biochem. 251, 613-621.

Kothakota, S., Azuma, T., Reinhard, C., Klippel, A., Tang, J., Chu, K., McGarry, T. J., Kirschner, M. W., Koths, K., Kwiatkowski, D. J. & Williams, L. T. (1997) Caspase-3 generated fragment of gelsolin: Effector of morphological change in apoptosis, Science. 278, 294-298.

Kurth, M. C. & Bryan, J. (1984) Platelet activation induces the formation of a stable gelsolin-actin complex from monomeric gelsolin, J. Biol. Chem. 259, 7473-7479.

Kwiatkowski, D. J., Janmey, P. A., Mole, J. E. & Yin, H. L. (1985) Isolation and properties of two actin-binding domains in gelsolin, J. Biol. Chem. 260, 15232-15238.

Kwiatkowski, D. J., Mehl, R., Izumo, S., Nadal-Ginard, N. & Yin, H. L. (1988a) Muscle is the major source of plasma gelsolin, J. Biol. Chem. 263, 8239-8243.

Kwiatkowski, D. J., Westbrook, C. A., Bruns, G. A. P. & Morton, C. C. (1988b) Localization of gelsolin proximal to ABL on chromosome 9., Am.J.Hum.Genet. 42, 565-572.

Kwiatkowski, D. J., Janmey, P. A. & Yin, H. L. (1989) Identification of critical functional and regulatory domains in gelsolin, J. Cell Biol. 108, 1717-1726.

Kwiatkowski, D. J., Stossel, T. P., Orkin, S. H., Mole, J. E., Colten, H. R. & Yin, H. L. (1986) Plasma and cytoplasmic gelsolins are encoded by a single gene and contain a duplicated actin-binding domain, Nature. 323, 455-458.

Kwiatkowski, D. J., Mehl, R. & Yin, H. L. (1988c) Genomic organization and biosynthesis of secreted and cytoplasmic forms of gelsolin, J. Cell Biol. 106, 375-384.

Kwiatkowski, D. J. (1999) Functions of gelsolin: motility, signaling, apoptosis, cancer, Curr.Op.Cell Biol. 11, 103-108.

Laham, L. E., Lamb, J. & Janmey, P. A. (1992) Nucleotide-dependent interactions between monomeric actin and gelsolin, Molecular Biology Of The Cell. 3, A 41-A 41.

Laham, L. E., Lamb, J. A., Allen, P. G. & Janmey, P. A. (1993) Selective binding of gelsolin to actin monomers containing ADP, J.Biol.Chem. 268, 14202-14207.

Laham, L. E., Way, M., Yin, H. L. & Janmey, P. A. (1995) Identification of two sites in gelsolin with different sensitivities to adenine nucleotides, Eur. J. Biochem. 234, 1-7.

Laine, R. O., Phaneuf, K. L., Cunningham, C. C., Kwiatkowski, D., Azuma, T. & Southwick, F. S. (1998) Gelsolin, a protein that caps the barbed ends and severs actin filaments, enhances the actin-based motility of Listeria monocytogenes in host cells., Infect.Immun. 66, 3775-3782.

Lamb, J. A., Allen, P. G., Tuan, B. Y. & Janmey, P. A. (1993) Modulation of gelsolin function - activation at low pH overrides Ca2+ requirement., Journal Of Biological Chemistry. 268, 8999-9004.

 Lamb, J., Allen, P. G., Tuan, B., Nakayama, T. & Janmey, P. A. (1992) Low pH activates gelsolin in the absence of calcium., Molecular Biology Of The Cell. 3, A 41-A 41.

Lee, W. M., Suhler, E., Lin, W. & Yin, H. (1993) Plasma gelsolin levels are decreased in acute liver-failure myocardial-infarction, septic shock and myonecrosis, Hepatology. 18, 317.

Linder, E. & Thors, C. (1992) Schistosoma-mansoni - praziquantel-induced tegumental lesion exposes actin of surface spines and allows binding of actin depolymerizing factor, gelsolin, Parasitology. 105, 71-79.

Lind, S. E., Janmey, P. A., Chaponnier, C., Herbert, T. J. & Stossel, T. P. (1987) Reversible binding of actin to gelsolin and profilin in human-platelet extracts, J.Cell Biol. 105, 833-842.

Liu, Y.-T. & Yin, H. L. (1998) Identification of the binding partners for flightless I, a novel protein bridging the leucine-rich repeat and the gelsolin superfamilies, J.Biol.Chem. 273, 7920-7927.

Lin, K.-M., Mejillano, M. & Yin, H. L. (2000) Ca2+ regulation of gelsolin by its C-terminal tail, J.Biol.Chem. 275.

Lück, A., D'Haese, J. & Hinssen, H. (1995) A gelsolin-related protein from lobster muscle:cloning, sequence analysis and expression., Biochem. J. 305, 767-775.

Lueck, A., Brown, D. & Kwiatkowski, D. J. (1998) The actin-binding proteins adseverin and gelsolin are both highly expressed but differentially localized in kidney and intestine, J.Cell Sci. 111, 3633-3643.

Lueck, A., Yin, H. L., Kwiatkowski, D. J. & Allen, P. G. (2000) Calcium regulation of gelsolin and adseverin: a natural test of the helix latch hypothesis., Biochemistry. 39, 5274-5279.

Lu, M., Witke, W., Kwiatkowski, D. J. & Kosik, K. S. (1997) Delayed retraction of filopodia in gelsolin nill mice, J.Cell Biol. 138, 1279-1287.

Maciver, S. K., Ternent, D. & McLaughlin, P. J. (2000) Domain 2 of gelsolin binds directly to tropomyosin, FEBS letters. 473, 71-75.

Mannherz, H. G., Gooch, J., Way, M., A. G. Weeds & McLaughlin, P. J. (1992) Crystallization of the Complex of Actin with Gelsolin Segment 1, J Mol Biol. 226, 899-901.

Mannherz, H. G., Mclaughlin, P., Gooch, J., Hesterkamp, T. & Weeds, A. G. (1994) Crystal-structure of the actin-gelsolin segment-1 complex at 2.5 angstrom and the orientation of the actin monomers in the gelsolin-actin(2) complex, Journal Of Muscle Research And Cell Motility. 15, 195-196.

Matsudaira, P.T. (1992) Expression and localization of villin, fimbrin, and myosin I in differentaiting F9 teratocarcinoma cells. Devlopmental Biol. 151, 575-585.

Maury, C. P. J. (1990) Isolation and characterization of cardiac amyloid in familial amyloid polyneuropathy type IV (Finnish): relation of the amyloid protein to variant gelsolin., Biochem. Biophys. Acta. 1096, 84-86.

Maury, C. P. J., Kere, J., Tolvanen, R. & Chapelle, A. d. l. (1990) Finnish hereditary amyloidosis is caused by a single nucleotide substitution in the gelsolin gene, FEBS Lett. 276, 75-77.

Maury, C. P. J., Alli, K. & Baumann, M. (1990) Finnish hereditary amyloidosis: amino acid sequence homology between the amyloid fibril protein and human plasma gelsolin., FEBS Lett. 260, 85-87.

Maury, C. P. J. (1991) Gelsolin-related amyloidosis, J.Clin. Invest. 87, 1195-1199.

Maury, C. P. J. & Nurmiaho-Lassila, E.-L. (1992) Creation of Amyloid fibrils from mutant Asn187 gelsolin peptides, Biochem. Biophys. Res. Comm. 183, 227-231.

Maury, C. P. J., Kere, J., Tolvanen, R. & Chapelle, A. d. l. (1992) Homozygosity for the Asn187 gelsolin mutation in Finnish-type familial amyloidosis is associated with severe renal disease., Genomics. 13, 902-903.

Maury, C. P. J. & Rossi, H. (1993) Demonstration of a circulating 65K gelsolin variant specific for familial amyloidosis, Finnish type, Biochem. Biophys. Res. Comm. 191, 41-44.

Maury, C. P. J. (1993) Homozygous familial amyloidosis, finnish type - demonstration of glomerular gelsolin-derived amyloid and nonamyloid tubular gelsolin, Clinical Nephrology. 40, 53-56.

Maury, C., Nurmiaholassila, E. L. & Rossi, H. (1994) Amyloid fibril formation in gelsolin-derived amyloidosis - definition of the amyloidogenic region and evidence of accelerated amyloid formation of mutant asn-187 and tyr-187 gelsolin peptides, Laboratory Investigation. 70, 558-564.

McGough, A. (1998) F-actin binding proteins, Curr.Op.Struct.Biol. 8, 166-176.

McGough, A., Chiu, W. & Way, M. (1998) Determination of the gelsolin binding site on F-actin: Implications for severing and capping., Biophys.J. 74, 764-772.

McLaughlin, P. J. & Gooch, J. (1992) Crystallization of human gelsolin., FEBS Lett. 302, 253-255.

McLaughlin, P. J., Gooch, J. T., Mannherz, H. G. & Weeds, A. G. (1993) Structure of gelsolin segment-1-actin complex and the mechanism of filament severing, Nature. 364, 685-692.

Meerschaert, K., DeCorte, V., DeVille, Y., Vandekerckhove, J. & Gettemans, J. (1998) Gelsolin and functionally similar actin-binding proteins are regulated by lysophosphatidic acid, EMBO J. 17, 5923-5932.

Mielnicki, L. M., Ying, A. M., Head, K. L., Asch, H. L. & Asch, B. B. (1999) Epigenetic regulation of gelsolin expression in human breast cancer cells., Exp.Cell Res. 249, 161-176.

Miyamoto, S., Funatsu, T., Ishiwata, S. & Fujime, S. (1993) Changes in mobility of chromaffin granules in actin network with its assembly and Ca2+-dependent disassembly by gelsolin, Biophys. J. 64.

Müllauer, L., Fujita, H., Ishizaki, A. & Kuzumaki, N. (1993) Tumor-suppressive function of mutated gelsolin in ras-transformed cells, Oncogene. 8, 2531-2536.

Nakamura, S., Sakurai, T. & Nonomura, Y. (1994) Differential expression of bovine adseverin in adrenal-gland revealed by in-situ hybridization - cloning of a cDNA for adseverin, J. Biol. Chem. 269, 5890-5896.

Nowak, E., Hinssen, H. & Dabrowska, R. (1993) Synergistic and antagonistic modulation of actomyosin ATPase by caldesmon, tropomyosin and gelsolin, J.Muscle Res.Cell Motil. 14, 244.

Ohtsu, M., Sakai, N., Fujita, H., Kashiwagi, M., Gasa, S., Shimizu, S., Eguchi, Y., Tsujimoto, Y., Sakiyama, Y., Kobayashi, K. & Kuzumaki, N. (1997) Inhibition of apoptosis by the actin-regulatory protein gelsolin, EMBO J. 16, 4650-4656.

Onoda, K. & Yin, H.L. (1993). gCap39 is phosphorylated. J.Biol.Chem. 268, 4106-4112.

Osborn, N, Weber, K., Naib Majani, W., Hinssen, H., Stockem, W. and Wohlfarth Bottermann. (1983). Immunocytochemistry of the acellular slime mold Physarum polycephalum.  III. Distrubution of myosin and the actin modulating protein (fragmin) in sandwiched plasmodia. Eur.J.Cell Biol. 29, 179-186.

Patkowski, A., Seils, J., Hinssen, H. & Dorfmuller, T. (1990) Size, shape parameters and calcium-induced conformational change of the gelsolin molecule. A dynamic light scattering study., Biopolymers. 30, 427-435.

Paunio, T., Kangas, H., Kalkkinen, N., Haltia, M., Palo, J. & Peltonen, L. (1994) Toward understanding the pathogenic mechanisms in gelsolin-related amyloidosis: in vitro expression reveals an abnormal gelsolin fragment., Human Mol. Genetics. 3, 2223-2229.

Pope, B., Way, M. & Weeds, A. G. (1991) Two of the three actin-binding domains of gelsolin bind to the same subdomain of actin, FEBS Lett. 280, 70-74.

Pope, B. & Weeds, A. G. (1986) Binding of pig plasma gelsolin to F-actin and partial fractionation into calcium-dependent and calcium-independent forms, Eur. J. Biochem. 161, 85-93.

Pope, B., Gooch, J., Hinssen, H. & Weeds, A. G. (1989) Loss of calcium sensitivity of plasma gelsolin is associated with the presence of calcium ions during preparation., FEBS Lett. 259, 185-188.

Pope, B., Maciver, S. & Weeds, A. G. (1995) Localization of the calcium-sensitive actin monomer binding site in gelsolin to segment 4 and identification of calcium-binding sites., Biochemistry. 34, 1583-1588.

Pope, B. J. Probing the effects of calcium on Gelsolin, Biochemistry. 36, 15848-15855.

Prendergast, G. C. & Ziff, E. B. (1991) Mbh1: a novel gelsolin/severin-related protein which binds actin in vitro and exhibits nuclear localization in vivo, EMBO Journal. 10, 757-766.

Prochniewicz, E., Zhang, Q., Janmey, P. & Thomas, D. D. (1994) Gelsolin - a new tool to study dynamics of actin, Biophysical Journal. 66, 194.

Prochniewicz, E., Zhang, Q., Janmey, P. & Thomas, D. (1996) Cooperativity in F-actin: binding of gelsolin at the barbed end affects structure and dynamics of the whole filament, J. Mol. Biol. 260, 756-766.

Puius, Y. A., Fedorov, E. V., Eichinger, L., Schleicher, M. & Almo, S. C. (2000) Mapping the functional surface of domain 2 in the gelsolin superfamily., Biochemistry. 39, 5322-5331.

Reid, S. W., Koepf, E. K. & Burtnick, L. D. (1993) Fluorescent responses of acrylodan-labeled plasma gelsolin, Archives Of Biochemistry And Biophysics. 302, 31-36.

Robbens, J., Louahed, J., De Pestel, K., Van Colen, I., Ampe, C., Vandekerckhove, J. & Renauld, J.-C. (1998) Murine adseverin (D5), a novel member of the gelsolin family, and murine adseverin are induced by interleukin-9 in T-helper lymphocytes., Mol.Cell.Biol. 18, 4589-4596.

Robinson, R. C., mejillano, M., Le, V. P., Burtnick, L. D., Yin, H. L. & Choe, S. (1999) Domain movement in gelsolin: a calcium-activated switch., Sicence. 286, 1939-1942.

Rodrigues, M. M., Rajagopalan, S., Jones, K., Nirankari, V., Wisniewski, T., Frangione, B. & Gorevic, P. D. (1993) Gelsolin immunoreactivity in corneal amyloid, wound-healing, and macular and granular dystrophies, Am. J. Ophthalmology. 115, 644-652.

Rouayrenc, J.-P., Fattoum, A., Mégean, C. & Kassab, R. (1986) Characterization of the Ca2+-induced conformational change in gelsolin and identification of interaction regions between actin and gelsolin., Biochemistry. 25, 3859-3867.

Ruiz Silva, B. & Burtnick, L. (1990) Characterization of horse plasma gelsolin, Biochem. Cell Biol. 68, 796-800.

Sakurai, T., Ohmi, K., Kurokawa, H. & Nonomura, Y. (1990) Distribution of a gelsolin-like 74,000 mol. wt protein in neural and endocrine tissues, Neuroscience. 38, 743-56.

Sakurai, T., Kurokawa, H. & Nonomura, Y. (1991) Comparison between the Gelsolin and Adseverin Domain Structure, The Journal of Biological Chemistry. 266, 15979-15983.

Salazar, R., Bell, S. E. & Davis, G. E. (1999) Coordinate induction of the actin cytoskeletal regulatory proteins gelsolin, Vasodilator-stimulated phosphoprotein, and profilin during capillary morphogenesis in vitro., Exp.Cell Res. 249, 22-32.

Schoepper, B. & Wegner, A. (1992) Gelsolin Binds to Polymeric Actin at a low Rate, J Biol Chem. 267, 13924-13927.

Schoepper, B. & Wegner, A. (1991) Rate Constants and Equilibrium Constants for Binding of Actin to the 1:1 Gelsolin-actin Complex, Eur J Biochem. 202, 1127-1131.

Scholz, A. & Hinssen, H. (1993) Biphasic pattern of gelsolin expression and gelsolin-actin interactions during myogenesis, J.Muscle Res.Cell Motil. 14, 277.

Selden, L. A., Kinosian, H. J., Newman, J., Lincoln, B., Hurwitz, C., Gershman, L. C. & Estes, J. E. (1998) Severing of F-actin by the aminoterminus half of gelsolin suggests internal cooperativity in gelsolin, Biophys. J. 75, 3092-3100.

Selve, N. & Wegner, A. (1986) Rate constants and equilbrium constants for binding of the gelsolin-actin complex to the barbed ends of actin filaments in the presence and absence of calcium, Eur. J. Biochem. 160, 379-387.

Selve, N. & Wegner, A. (1987) pH-dependent rate of formation of the gelsolin-actin complex from gelsolin and monomeric actin, Eur. J. Biochem. 161, 111-115.

Shaw, T. J., Terry, V., Shorey, C. D. & Murphy, C. R. (1998) Alterations in distribution of actin binding proteins in uterine stromal cells during decidualization in the rat., Cell Biol.Internat. 22, 237-243.

Southwick, F. S. (2000) Gelsolin and ADF/cofilin enhance the actin dynamics of motile cells., PNAS. 97, 6936-6938.

Steed, P. M., Nagar, S. & Wennogle, L. P. (1996) Phospholipase D regulation by a physical interaction with the actin-binding protein gelsolin., Biochemistry. 35, 5229-5237.

Stella, M. C., Schauerte, H., Straub, K. L. & Leptin, M. (1994) Identification of secreted and cytosolic gelsolin in Drosophila., J. Cell Biol. 125, 607-616.

Straub, K. L., Stella, M. C. & Leptin, M. (1996) The gelsolin-related flightless I protein is required for actin distribution during cellularisation in Drosophila, J. Cell Sci. 109, 263-270.

Sun, H. Q., Wooten, D. C., Janmey, P. A. & Yin, H. L. (1994) The actin side-binding domain of gelsolin also caps actin-filaments - implications for actin filament severing, J. Biol. Chem. 269, 9473-9479.

Sun, H. Q., Yamamoto, M., Mejillano, M. & Yin, H. L. (1999) Gelsolin, a multifunctional actin regulatory protein., J.Biol.Chem. 274, 33179-33182.

Sunada, Y., Shimizu, T., Nakase, H., Ohta, S., Asaoka, T., Amano, S., Sawa, M., Kagawa, Y., Kanazawa, I. & Mannen, T. (1993) Inherited amyloid polyneuropathy type-iv (gelsolin variant) in a Japanese family, Annals Of Neurology. 33, 57-62.

Sun, H., Lin, K. & Yin, H. L. (1997) Gelsolin modulates phosphlipase C activity In Vivo through phospholipid binding, J.Cell Biol. 138, 811-820.

Tanaka, J., Kira, M. & Sobue, K. (1993) Gelsolin is localized in neuronal growth cones, Developmental Brain Research. 76, 268-271.

Tanaka, J. & Sobue, K. (1994) Localization and characterization of gelsolin in nervous tissue: gelsolin is specifically enriched in myelin-forming cells., J. Neuroscience. 14, 1038-1052.

Tellam, R. L. (1986) Gelsolin inhibits nucleotide exchange from actin, Biochemistry. 25, 5799-5804.

Tellam, R. & Frieden, C. (1982) Cytochalasin D and platelet gelsolin accelerate actin polymer formation. A model for regulation of the extent of actin polymer formation in vitro., Biochemistry. 21, 3207-3214.

Teubner, A., Sobekklocke, I., Hinssen, H. & Eichenlaubritter, U. (1993) Expression and distribution of actin and gelsolin in the ovary of the mouse, Journal Of Muscle Research And Cell Motility. 14, 243.

Teubner, A., Sobekklocke, I., Hinssen, H. & Eichenlaubritter, U. (1994) Distribution of gelsolin in mouse ovary, Cell And Tissue Research. 276, 535-544.

Thorstensson, R., Utter, G., Norberg, R., Fagraeous, A., Hartwig, J. H., Yin, H. L. & Stossel, T. P. (1982) Distribution of actin, myosin, actin binding protein and gelsolin in cultured lymphoid cells, Expt.Cell Res. 140, 395-400.

Tuominen, E. K. J., Holopainen, J. M., Chen, J., Prestwich, G. D., Bachiller, P. R., Kinnunen, P. K. J. & Janmey, P. J. (1999) Fluorescent phosphoinositide derivatives reveal specific binding of gelsolin and other actin regulatory proteins to mixed lipid bilayers., Eur.J.Biochem. 263, 85-92.

T'Jampens, D., Meerschaert, K., Constantin, B., Bailey, J., Cook, L. J., De Corte, V., De Mol, H., Goethals, M., Van Damme, J., Vandekerckhove, J. & Gettemans, J. (1997) Molecualr cloning, overexpression, developmental regulation and immunolocalization of fragmin P, a gelsolin-related actin binding protein from Physarum polycephalum plasmodia, J.Cell Sci. 110, 1215-1226.

Vandekerckhove, J., Bauw, G., Vancompernolle, K., Honore, B. & Celis, J. (1990) Comparative two dimentional gel analysis and microsequencing identifies gelsolin as one of the most prominent downregulated markers of transformed human fibroblasts and epithelial cells., J. Cell Biol. 111, 95-102.

Van Troys, M., Dewitte, D., Verschelde, J.-L., Goethals, M., Vandekerckhove, J. & Ampe, C. (1997) Analogous F-actin binding by cofilin and gelsolin segment 2 substantiates their structural relationship, J.Biol.Chem. 272, 3275-32758.

Van Troys, M., Dewitte, D., Goethals, M., Vandekerckhove, J. & Ampe, C. (1996) Evidence for an actin binding helix in gelsolin segment 2; have homologous sequences in segments 1 and 2 of gelsolin evolved to divergent actin binding functions?, FEBS letters. 397, 191-196.

Vasconcellos, C. A. & Lind, S. E. (1993) Coordinated inhibition of actin-induced platelet-aggregation by plasma gelsolin and vitamin-D-binding protein, Blood. 82, 3648-3657.

Vasconcellos, C., Drazen, J., Janmey, P. A., Wohl, M. E., Lind, S. E. & Stossel, T. P. (1993) Gelsolin reduces the viscosity of cystic-fibrosis sputum invitro, Clinical Research. 41, A 283-A 283.

Vasconcellos, C. A., Allen, P. G., Wohl, M. E., Drazen, J. M., Janmey, P. A. & Stossel, T. P. (1994) Reduction in viscosity of cystic-fibrosis sputum in vitro by gelsolin, Science. 263, 969-971.

Vitale, M. L., Castillo, A. R. D., Tchakarov, L. & Trifaro, J.-M. (1991) Cortical Filamentous Actin Disassembly and Scinderin Redistribution during Chromaffin Cell Stimulation Precede Exocytosis, A Phenomenon Not Exhibited by Gelsolin, The Journal of Cell Biology. 113, 1058-1067.

Vouyiouklis, D. A. & Brophy, P. J. (1997) A novel gelsolin isoform expressed by oligodendrocytes in the central nervous system, J.Neurochem. 69, 995-1005.

Watts, R. G. & Howard, T. H. (1992) Evidence for a gelsolin-rich, labile F-actin pool in human polymorphonuclear leukocytes., Cell Mot. and Cytoskel. 21, 25-37.

Watts, R. G., Deaton, J. D. & Howard, T. H. (1995) Dynamics ot triton-insoluble and triton-soluble F-actin pools in calcium-activated human polymorphonuclear leukocytes: evidence for regulation by gelsolin., Cell Mot. and the Cytoskel. 30, 136-145.

Way, M. & Weeds, A. G. (1988) Nucleotide sequence of pig plasma gelsolin. Comparison of protein sequence with human gelsolin and other actin-severing proteins shows strong homologies and evidence for large internal repeats, J. Mol. Biol. 203, 1127-1133.

Way, M., Gooch, J., Pope, B. & Weeds, A. G. (1989) Expression of human plasma gelsolin in E. coli and dissection of actin binding sites by segmental deletion mutagenesis, J. Cell Biol. 109, 593-605.

Way, M., Pope, B., Gooch, J., Hawkins, M. & Weeds, A. G. (1990) Identification of a region of segment 1 of gelsolin critical for actin binding, EMBO J. 9, 4103-4109.

Way, M., Pope, B. & Weeds, A. G. (1991) Molecular biology of actin binding proteins: evidence for a common structural domain in the F-actin binding sites of gelsolin and alpha-actinin, J. Cell Sci. Supplement. 14, 91-94.

Way, M., Pope, B. & Weeds, A. G. (1992) Are the conserved sequences in segment 1 of gelsolin important for binding actin?, J. Cell Biol. 116, 1135-1143.

Way, M., Pope, B. & Weeds, A. G. (1992) Evidence for functional homology in the F-actin binding domains of gelsolin and alpha-actinin: implications for the requirements of severing and capping, J. Cell Biol. 119, 835-842.

Wang, E., Yin, H.L., Kreuger, J.G., Caliguri, L.A., Tamm, I. (1984).  Unphosphorylated gelsolin is localised in regions of cell-substratum contact or attachment in Rous sarcoma virus-transformed rat cells. J.Cell Biol. 98, 761-771.

Wang, J.-S., Coburn, J. P., Tauber, A. I. & Zaner, K. S. (1997) Role of gelsolin in actin depolymerization of adherent human neutrophils, Mol.Biol.Cell. 8, 121-128.

Weber, A., Pring, M., Lin, S.-L. & Bryan, J. (1991) Role of the N- and C-terminal actin-binding domains of gelsolin in barbed filament end capping, Biochemistry. 30, 9327-9334.

Weeds, A. G., Gooch, J., McLaughlin, P. & Maury, C. P. J. (1993) Variant plasma gelsolin responsible for familial amyloidosis (Finnish type) has defective actin severing activity., FEBS Lett. 335, 119-123.

Weeds, A. G., Gooch, J., McLaughlin, P., Pope, B., Bengtsdotter, M. & Karlsson, R. (1995) Identification of the trapped calcium in the gelsolin segment 1-actin complex: implications for the role of calcium in the control of gelsolin activity., FEBS Lett. 360, 227-230.

Weeds, A. G., Gooch, J., Pope, B. P. & Harris, H. E. (1986) Preparation and characterization of pig plasma and platelet gelsolins, Eur. J. Biochem. 161, 69-76

Weeds, A. G., Harris, H., Gratzer, W. B. & Gooch, J. (1986) Interactions of pig plasma gelsolin with G-actin, Eur. J. Biochem. 161, 77-84.

Wells, A., Ware, M. F., Allen, F. D. & Lauffenburger, D. A. (1999) Shaping up for shipping out: PLCg signaling of morphology changes in EGF-stimulated fibroblast migration., Cell Mot.Cytoskel. 44, 227-233.

Wen, D., Corina, K., Chow, E. P., Miller, S., Janmey, P. A. & Pepinsky, R. P. (1996) The plasma and cytoplasmic forms of human gelsolin differ in disulfide structure., Biochemistry. 35, 9700-9709.

Wille, M., Just, I., Wegner, A. & Aktorias, K. (1992) ADP-ribosylation of gelsolin-actin complexes by Clostridial toxins, J. Biol. Chem. 267, 50-55.

Wilkins, J. A., Schwartz, J. H. & Harris, D. A. (1983) Brevin, a serum protein that acts on the barbed ends of actin filaments., Cell Biol.International Rep. 1, 1097-1104.

Witke, W., Sharpe, A. H., HArtwig, J. H., Azuma, T., Stossel, T. P. & Kwiatkowski, D. J. (1995) Hemostatic, inflammatory and fibroblast responses are blunted in mice lacking gelsolin., Cell. 81, 41-51.

Wriggers, W., Tang, Z. X., Azuma, T., Marks, P. W. & Janmey, P. A. (1998) Cofilin and gelsolin segment-1: Molecular dynamics simulation and biochemical analysis predict a similar binding mode, J.Mol.Biol. 282, 921-932.

Wulfkuhle, J. D., Donina, I. E., Stark, N. H., Pope, R. K., Pestonjamasp, K. N., Niswonger, M. L. & Luna, E. J. (1999) Domain analyis of supervillin, an F-actin bundling plasma membrane protein with functional nuclear localization signals., J.Cell Sci. 112, 2125-2136.

Xian, W., Garver, T. M., Braunlin, W. H. & Janmey, P. A. (1992) Nmr and cd conformational studies of a 20 amino-acid PIP2-binding site on gelsolin, Faseb Journal. 6, A 87-A 87.

Xian, W. J., Braunlin, W. H. & Janmey, P. A. (1993) Cd and nmr-studies of the conformation of a 20-amino acid PIP2-binding domain of gelsolin in mixed-solvent, Biophysical Journal. 64, 62.

Xian, W., Vegners, R., Janmey, P. A. & Braunlin, W. H. (1995) Spectroscopic studies of a phosphoinositide-binding peptide from gelsolin: behavior in solutions of mixed solvent and anionic micelles, Biophys. J. 69, 2695-2702.

Yin, H. L. & Stossel, T. P. (1979) Control of cytoplasmic actin gel-sol transformation by gelsolin, a calcium dependent regulatory protein., Nature. 281, 583-586.

Yin, H. L. & Stossel, T. P. (1980) Purification and structural properties of gelsolin, a calcium-activated regulator protein of macrophages., J. Biol. Chem. 255, 9490-9493.

Yin, H. L., Hartwig, J. H., Maruyama, K. & Stossel, T. P. (1981) Ca2+ control of actin filament length. Effects of macrophage gelsolin on actin polymerization, J. Biol. Chem. 256, 9693-9697.

Yin, H. L. (1988) Gelsolin: calcium and polyphosphoinositide-regulated actin- modulating protein, Bioessays. 7, 176-179.

Yin, H. L., Iida, K. & Janmey, P. A. (1988) Identification of a polyphospho-inositide-modulated domain in gelsolin which binds to the sides of actin filaments, J. Cell Biol. 106, 805-812.

Yin, H. L., Janmey, P. A. & Schleicher, M. (1990) Severin is a gelsolin prototype, FEBS Lett. 264, 78-80.

Yu, F.-X., Zhou, D. & Yin, H. L. (1991) Chimeric and Truncated gCap39 Elucidate the Requirements for Actin Filament Severing and End Capping by the Gelsolin Family of Proteins, J. Biol. Chem. 266, 19269-19275.

Yu, F.-Z., Sun, H.-Q., Janmey, P. A. & Yin, H. L. (1992) Identification of a polyphosphoinositide-binding sequence in an actin monomer-binding domain of gelsolin, J. Biol. Chem. 267, 14616-14621.

Zapun, A., Grammatyka, S., Deral, G. & Vernet, T. (2000) Calcium-dependent conformational stability of modules 1 and 2 of human gelsolin., Biochem.J. 350, 873-881.

 

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