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Talin 

Page updated 10/6/02

Provides a link between actin microfilaments and the plasma membrane. Talin is a fairly large protein (actual mol.wt 270 kDa, but appears to be 235 kDa on gels), which gave it the original name of p235 (Collier & Wang 1982a,b).  When the first sequence became available (Rees et al, 1990) it was clear that talin belonged to the band 4.1 family, and was composed of an N-terminal globular domain and a .  Talin nucleates actin assembly and binds to vinculins in addition to a host of actin binding proteins and other proteins mainly at the focal adhesion (Table 1) (a).  As well as binding to vinculin which itself associated with lipids it has been reported that talin also is able to bind lipids directly (Goldmann et al, 1992; Dietrich et al, 1993).

 

Talin-binding protein Function Reference
actin component of microfilaments Kaufmann et al, 1991; Schmidt et al, 1999
pp125FAK A tyrosine protein kinase Chen et al, 1995; Borowsky & Hynes, 1998
layilin A trans-membranous glycoprotein Borowsky & Hynes, 1998
vinculin pivotal component of the focal contact Burridge & Mangeat, 1984; Bass et al, 2002
b-integrin Trans-membranous adhesion protein Horwitz et al, 1986; Burn et al,1988; Knezevic et al, 1996; Calderwood et al, 2002
Myosin II Contractile protein Lin et al, 1998
Dystrophin Giant protein absent in Duchenne Muscular Dystrophy . Senter et al, 1993
Table 1   Talin binding partners
 

The structure of Talin.
Talin has been shown to be a head-to tail dimeric protein that adopts a "dumbbell" shape by E.M. (
Goldmann et al, 1994). The protein is easily digested (thrombin, calpain II) into two domains 47kDa and a 200kDa (Niggli et al, 1994).  The 47kDa fragment  later determined to be the N-terminus (Rees et al, 1990) binds anionic lipids (Niggli et al, 1994), whereas the high helical content C-terminal tail forms a number of repeats (McLachlan et al, 1994).

The actin -binding sites of talin and the affects of the protein on actin polymerization and structure.
Talin is presently thought to contain three different actin binding sites (
Hemmings et al, 1996), through these talin has a complex relationship with actin.  On the one hand the early work concluded that talin reduced filament length (Collier & Wang, 1982a; Goldmann et al, 1994) and reduced the viscosity of actin solutions (Collier & Wang, 1982a), on the other talin has been found to nucleate actin assembly (Kaufmann et al, 1992).  The interaction between actin and talin is very pH sensitive (Schmidt et al, 1993; Goldmann et al, 1999).

 

The interaction of talin with vinculin 
Talin and vinculin are two pivotal components of the focal adhesion. The introduction of antibodies against talin to cells disrupts focal adhesion and the phosphorylation of vinculin by also disrupts focal adhesions (). The two proteins have been shown to interact (
Burridge & Mangeat, 1984), and there are three distinct vinculin binding sites on talin (Hemmings et al, 1996)

 

Other variant Talin molecules
In addition to the talin homolog TALA, Dictyostelium also has another talin-like molecule (TALB) that has a C-terminal extension that is homologous to the  villin headpiece domain (found in a number of other actin binding proteins) (
Tsujioka et al, 1999).

 

References:-

Adey, N. B. & Kay, B. K. (1997) Isolation of peptides from phage-displayed random peptide libraries that interact with the talin-binding domain of vinculin, Biochem. J. 324, 523-528.

Bass, M. D., Patel, B., Barsukov, I. G., Fillingham, I. J., Mason, R., Smith, B. J., Bagshaw, C. R. & Critchley, D. R. (2002) Further characterization of the interaction between the cytoskeletal proteins talin and vinculin. Biochem. J. 362, 761-768.

Bertagnolli, M. E., Locke, S. J., Hensler, M. E., Bray, P. F. & Beckerle, M. C. (1993) Talin distribution and phosphorylation in thrombin-activated platelets, J.Cell Sci. 106, 1189-1199.

Borowsky, M. L. & Hynes, R. O. (1998) Layilin, a novel talin-binding transmembranous protein homologous with C-type lectins, is localized in membrane ruffles. J.Cell Biol. 143, 429-442.

Bolton, S. J., Barry, S. T., Mosley, H., Patel, B., Jockusch, B. M., Wilkinson, J. M. & Critchley, D. R. (1997) Monoclonal antibodies recognizing the N-and C-terminal regions of talin disrupt actin stress fibres when microinjected into human fibroblasts., Cell Mot.Cytoskel. 36, 363-376.

Brown, M. J. & Shaw, S. (1999) T-cell activation: Interplay at the interface. Curr.Biol. 9, 26-28.

Bubeck, P., Pistor, S., Wehland, J. & Jockusch, B. M. (1997) Ligand recruitment by vinculin domains in transfected cells. J.Cell Sci. 110, 1361-1371.

Burn, P., Kupfer, A. & Singer, S. J. (1988) Dynamic membrane-cytoskeletal interactions: specific association of integrin and talin arises in vivo after phorbol ester treatment of peripheral blood lymphocytes. Proc.Nat.Acad.Sci.USA. 85, 497-501.

Burridge, K. & Connell, L. (1984) A new protein of adhesion plaques and ruffling membranes. J.Cell Biol. 97, 359-367.

Burridge, K. & Mangeat, P. (1984) An interaction between vinculin and talin. Nature. 308, 744-746.

Calderwood, D. A., Yan, B., de Pereda, J. M., Alvarez, B. G., Fujioka, Y., Liddington, R. C. & Ginsberg, M. H. (2002) The phosphotyrosine binding-like domain of talin activates integrins.  J.Biol.Chem. 277, 21749-21758.

Chen, H.-C., Appeddu, P. A., Parsons, J. T., Hildebrand, J. D., Schaller, M. D. & Guan, J.-L. (1995) Interaction of focal adhesion kinase with cytoskeletal protein talin. J. Biol. Chem. 270, 16995-16999.

Critchley, D. R. (2000) Focal adhesions - the cytoskeletal connection. Curr.Op.Cell Biol. 12, 133-139.

Crenshaw, H. C., Allen, J. A., Skeen, V., Harris, A. & Salmon, E. D. (1996) Hydrostatic pressure has different effects on the assembly of tubulin, actin, myosinII, vinculin, talin, vimentin, and cytokeratin in mammalian tissue cells. Exp.Cell Res. 227, 285-297.

Collier, N. C. & Wang, K. (1982a) Human platelet p235: a high Mr protein which restricts the length of actin filaments. FEBS letters. 143, 205-210.

Collier, N. C. & Wang, K. (1982b) Purification and properties of human platelet p235. J.Biol.Chem. 257, 6937-6943.

DePasquale, J. A. & Izzard, C. S. (1991) Accumulation of talin in nodes at the edge of the lammellipodium and separate incorporation into adhesion plaques at focal contacts in fibroblasts, J.Cell Biol. 113, 1351-1359.

Dietrich, C., Goldmann, W. H., Sackmann, E. & Isenberg, G. (1993) Interaction of NBD-talin with lipid monolayers, FEBS letters. 324, 37-40.

Dustin, M. L., Olszowy, M. W., Holdorf, A. D., Li, J., Bromley, S., Desai, N., Widder, P., Rosenberger, F., Anton van der Merwe, P., Allen, P. M. & Shaw, A. S. (1998) A novel adaptor protein orchestrates receptors patterning and cytoskeletal polarity in T-cell contacts., Cell. 94, 667-677.

Fox, J. E. B., Goll, D. E., Reynolds, C. C. & Phillips, D. R. (1985) Idnetification of two proteins (actin-binding protein and p235) that are hydrolyzed by endogenous Ca2+-dependent protease during platelet aggregation, J.Biol.Chem. 260, 1060-1066.

Fukui, Y., de Hostos, E., Yumura, S., Kitanishi-Yumura, T. & Inoué, S. (1999) Architectural dynamics of F-actin in eupodia suggests their role in invasive locomotion in Dictyostelium., Exp.Cell Res. 249, 33-45.

Gilmore, A. P., Wood, C., Ohanian, V., Jackson, P., Patel, B., Rees, D. J. G., Hynes, R. O. & Critchley, D. R. (1992) The cytoskeletal protein talin contains at least 2 distinct vinculin binding domains., J. Cell Biol. 122, 337-347.

Gilmore, A., Jackson, P., Waites, G. & Critchley, D. (1992) Further characterization of the talin-binding site in the cytoskeletal protein vinculin., J. Cell Sci. 103, 719-731.

Gilmore, A. & Burridge, K. (1996) Regulation of vinculin binding to talin and actin by phosphatidyl-inositol-4-5-bisphosphate. Nature. 381, 531-535.

Goldmann, W. H., Guttenberg, Z., Kaufmann, S., Hess, D., Ezzel, R. M. & Isenberg, G. (1997) Examinating F-actin interaction with talin and talin head and tail fragment using static and dynamic light scattering, Eur.J.Biochem. 250, 447-450.

Goldmann, W. H., Niggli, V., Kaufmann, S. & Isenberg, G. (1992) Probing actin and liposome interaction of talin and talin-vinculin complexes: a kinetic, thermodynamic and lipid labeling study, Biochemistry. 31, 7665-7671.

Goldmann, W. H., Bremer, A., Häner, M., Aebi, U. & Isenberg, G. (1994) Native talin is a dumbbell-shaped homodimer when it interacts with actin, J.Struct.Biol. 112, 3-10.

Goldmann, W. H. & Isenberg, G. (1991) Kinetic determination of talin-actin binding, Biochem.Biophys.Res.Comm. 178, 718-723.

Goldmann, W. H., Käs, J. & Isenberg, G. (1993) Talin decreases the bending elasticity of actin filaments, Biochem.Soc.Transactions. 22, 46s.4.

Goldmann, W. H., Hess, D. & Isenberg, G. (1999) The effect of intact talin and talin tail fragement on actin filament dynamics and structure depends on pH and ionic strength., Eur.J.Biochem. 260, 439-445.

Goldmann, W. H., Senger, R., Kafmann, S. & Isenberg, G. (1995) Determination of the affinity of talin and vinculin to charged lipid vesicles: a light scatter study, FEBS letters. 368, 516-518.

Hemmings, L., Rees, D. L. G., Ohanian, V., Bolton, S. J., Gilmore, A. P., Patel, B., Priddle, H., Trevithick, J. E., Hynes, R. O. & Critchley, D. R. (1996) Talin contains three actin-binding sites each of which is adjacent to a vinculin-binding site. J.Cell Sci. 109, 2715-2726.

Holtzman, D. A., Yang, S. & Drubin, D. G. (1993) Synthetic-lethal interactions identify two novel genes, SLA1 and SLA2, that control membrane cytoskeleton assembly in Saccharomyces cerevisiae. J.Cell Biol. 122, 635-644.

Horwitz, A., Duggan, K., Buck, C., Beckerle, M. & Burridge, K. (1996) Interaction of plasma membrane fibronectin receptor with talin - a transmembrane linkage., Nature. 320, 531-533.

Isenberg, G., Niggli, V., Pieper, U., Kaufmann, S. & Goldmann, W. H. (1996) Probing phosphatidylinostiolphosphates and adenosinenucleotides on talin nucleated actin polymerization. FEBS letters. 397, 316-320.

Isenberg, G. & Goldmann, W. H. (1992) Actin-membrane coupling: a role for talin. J.Muscle Res.Cell Mot. 13, 587-589.

Isenberg, G. & Goldmann, W. H. (1998) Peptide-specific antibodies localize the major lipid binding sites of talin dimers to opposite arranged N-terminal 47kDa subunits. FEBS letters. 426, 165-170.

Johnson, R. & Craig, S. (1994) An intramolecular association between the head and tail domains of vinculin modulates talin binding. J. Biol. Chem. 269, 12611-12619.

Kaufmann, S., Piekenbrock, T., W. H. Goldmann , Barmann, M. & Isenberg, G. (1991) Talin binds to Actin and Promotes Filament Nucleation. FEBS Lett. 284, 187-191.

Kaufmann, S., Käs, J., Goldmann, W. H., Sackmann, E. & Isenberg, G. (1992) Talin anchors and nucleates actin filaments at lipid membranes. FEBS letters. 314, 203-205.

Knezevic, I., Leisner, T. M. & Lam, S. C.-T. (1996) Direct binding of the platelet integrin aIIbb3 (GPIIB-IIIa) to talin. Evidence that interaction is mediated through the cytoplasmic domains of both aIIb and b3. J.Biol.Chem. 271, 6104-6109.

Korneeva, N. & Jockusch, B. M. (1996) Light microscopic analysis of ligand-induced actin filament suprastructures. Eur.J. Cell Biol. 71, 351-355.

Kreitmeier, M., Gerisch, G., Heizer, C. & Müller-Taubenberger, A. (1995) A talin homologue of Dictyostelium rapidly assembles at the leading edge of cells in response to chemoattractant, J. Cell Biol. 129, 179-188.

Lee, S.-W. & Otto, J. J. (1996) Differences in turnover rates of vinculin and talin caused by viral transformation and cell density. Exp.Cell Res. 227, 352-359.

Lee, S.-W. & Otto, J. T. (1997) Vinculin and talin: kinetics of entry and exit from the cytoskeletal pool. Cell Mot.Cytoskeleton. 36, 101-111.

Lin, Y., Kishi, H., Nakamura, A., Takagi, T. & Kohama, K. (1998) N-terminal myosin-binding fragment of talin. Biochem.Biophys.Res.Comm. 249, 656-659.

Lee, T.-Y. J. L. & Gotlieb, A. I. (1999) Early stages of endothelial wound repair: conversion of quiescent to migrating endothelial cells involves tyrosine phosphorylation and actin microfilament reorganization. Cell Tiss.Res. 297, 435-450.

McLachlan, A. D., Stewart, M., Hynes, R. O. & Rees, D. J. G. (1994) Analysis of repeat motifs in the talin rod.  J.Mol.Biol. 235, 1278-1290.

Moulder, G. L., Huang, M. M., Waterston, R. H. & Barstead, R. J. (1996) Talin requires b-integrin, but not vinculin, for its assembly into focal adhesion-like structures in the nematode Caenorhabditis elegansMol.Biol.Cell. 7, 1181-1193.

Muguruma, M., Matsumura, S. & Fukazawa, T. (1992) Augmentation of a-actinin-induced gelation of actin by talin.  J.Biol.Chem. 267, 5621-5624.

Muguruma, M., Nishimuta, S., Tomisaka, Y., Ito, T. & Matsumura, S. (1995) Organization of the functional domains in membrane cytoskeletal protein talin. J. Biochem. 117, 1036-1042.

Niewöhner, J., Weber, I., Maniak, M., Müller-Taubenberger, A. & Gerisch, G. (1997) Talin-null cells of Dictyostelium are strongly defective in adhesion to particle and substrate surfaces and slightly impaired in cytokinesis. J.Cell Biol. 138, 349-361.

Niggli, V., Kaufmann, S., Goldmann, W. H., Weber, T. & Isenberg, G. (1994) Identification of functional domains in the cytoskeletal protein talin. Eur.J.Biochem. 224, 951-957.

Nuckolls, G. H., Romer, L. H. & Burridge, K. (1992) Microinjection of antibodies against talin inhibits the spreading and migration of fibroblasts.  J.Cell Sci. 102, 753-762.

Nuckolls, G. H., Turner, C. E. & Burridge, K. (1990) Functional studies of the domains of talin. J.Cell Biol. 110, 1635-164

Patil, S., Jedsadayanmata, A., Wencel-Drake, J. D., Wang, W., Knezevic, I. & Lam, S. C.-T. (1999) Identifiaction of a talin-binding site in the integrinb3 subunit distinct from the NPLY regulatory motif of post-ligand binding functions. J.Biol.Chem. 274, 28575-28583.

Penninger, J. M. & Crabtree, G. R. (1999) The actin cytoskeleton and lymphocyte activation, Cell. 96, 9-12.

Priddle, H., Hemmings, L., Monkley, S., Woods, A., Patel, B., Sutton, D., Dunn, G. A., Zicha, D. & Critchley, D. R. (1998) Disruption of the talin gene compromises focal adhesion assembly in undifferentiated but not differentiated embryonic stem cells. J.Cell Biol. 142, 1121-1133.

Rees, D. J. G., Ades, S. E., Singer, S. J. & Hynes, R. O. (1990) Sequence and domain structure of talin. Nature. 347, 685-689.

Ruddies, R., Goldmann, W. H., Isenberg, G. & Sackmann, E. (1993) The viscoelasticity of entangled actin networks: the influence of defects and modulation by talin and vinculin, Eur.Biophys.J. 22, 309-321.

Rønnov-Jessen, L. & Petersen, O. W. (1996) A function for filamentous a-smooth muscle actin: Retardation of motility in fibroblasts. J.Cell Biol. 134, 67-80.

Sanger, J. M., Dome, J. S., Hock, R. S., Mittal, B. & Sanger, J. W. (1994) Occurrence of fibers and their association with talin in the cleavage furrows of PtK2 cells. Cell Mot.Cytoskeleton. 27, 26-40.

Schmidt, J. M., Robson, R. M., Zhang, J. & Stromer, M. H. (1993) The marked pH dependence of the talin-actin interaction. Biochem.Biophys.Res.Comm. 197, 660-666.

Simson, R., Wallraff, E., Faix, J., Niewöhner, J., Gerisch, G. & Sackmann, E. (1998) Membrane bending modulus and adhesion energy of wild-type and mutant cells of Dictyostelium lacking talin or cortexillins. Biophys.J. 74, 514-522.

Schmidt, J. M., Zhang, J., Lee, H.-S., Stromer, M. H. & Robson, R. M. (1999) Interaction of talin with actin: Sensitive modulation of filament crosslinking activity. Arch.Biochem.Biophys. 366, 139-150.

Senter, L., Luise, M., Presotto, C., Betto, R., Teresi, A., Ceoldo, S. & Salviati, G. (1993) Interaction of dystrophin with cytoskeletal proteins: Binding to talin and actin., Biochem.Biophys.Res.Comm. 192, 899-904.

Takeuchi, K., Kawashima, A., Nagafuchi, A. & Tsukita, S. (1994) Structural diversity of band 4.1 superfamily members, J.Cell Sci. 107, 1921-1928.

Tempel, M., Goldmann, W. H., Isenberg, G. & Sackmann, E. (1995) Interaction of the 47-kDa talin fragment and the 32-kDa vinculin fragment with acidic phospholipids: a computer analysis, Biophys.J. 69, 228-241.

Tranqui, L. & Block, M. R. (1995) Intracellular processing of talin occurs within focal adhesions, Exp.Cell.Res. 217, 149-156.

Tsujioka, M., Machesky, L. M., Cole, S. L., Yahata, K. & Inouye, K. (1999) A unique talin homologue with a villin headpiece-like domain is required for multicellular morphogenisis in Dictyostelium. Current Biol. 9, 389-392.

Vignoud, L., Albigès-Rizo, C., Frachet, P. & Block, M. R. (1997) NPXY motifs control the recruitment of the a5b1 intergrin in focal adhesions independently of the association of talin with the b1 chain, J.Cell Sci. 110, 1421-1430.

Watters, D., Garrone, B., Gobert, G., Williams, S., Gardiner, R. & Lavin, M. (1996) Bisratene A causes phosphorylation of talin and redistribution of actin filaments in fibroblasts: possible role for PKC-d., Exp.Cell Res. 229, 327-335.

Zhang, J., Robson, R. M., Schmidt, J. M. & Stromer, M. H. (1996) Talin can crosslink actin filaments into both networks and bundles, Biochem.Biophys.Res.Comm. 218, 530-537.

 
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