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The Cleavage Furrow (contractile ring) and Cytokinesis

Page updated 27/1/03

The cleavage furrow is an actin rich "purse string" that draws tight to separate daughter cells to complete cytokinesis in cell division.  Early work established that the contractile ring was composed of filaments (Schroeder, 1968), which were later identified as being of actin (Perry et al, 1971; Schroeder, 1973) and myosin II (Fujiwara & Pollard, 1976).  Since then a host of actin binding proteins and other cytoskeletal proteins have been identified as being constituents of the cleavage furrow.   See Table 1 for a list of actin binding proteins known, or suspected of being involved in cleavage formation and function, and Table 2 for another (shorter), list of actin binding proteins for which there is evidence (usually the failure to co-localise to the cleavage furrow) against an involvement.  More information on each of the individual actin-binding proteins is available from the Encyclopaedia of ABPs. It is important to note that the actin -binding proteins listed in table 1 are necessary for classic cytokinesis not traction mediated cytokinesis (see below for the distinction).  In most cases these ABPs role in traction mediated cytokinesis has not been tested.  Yeasts both fission (Schizosaccharomyces pombe) and budding (Saccharomyces cerevisiae) are similar enough to reveal details of animal cytokinesis. Plants do things rather differently and Plant Cytokinesis is discussed separately as is Bacterial Cytokinesis.  When cytokinesis goes wrong this can result in unequal separation of chromosomes leading to genetic instability and cancer (Cytokinesis & Cancer).  Asymmetric cytokinesis is important for morphogenesis in development.

Actin-binding Protein Function Reference
Myosin II Contraction of the cleavage furrow de Lozanne & Spudich, 1987; Robinson et al, 2002
Myosin V Involved in cytokinesis of fission yeast Win et al, 2000
CAP Adenylyl cyclase activating protein Noegel et al, 1999
Cortexillin A bundling protein Weber et al, 2000; Faix et al, 1996
Coronin A bundling protein de Hostos et al, 1993; Fukui et al, 1999
Profilin A G-actin binding protein. a component of the Arp2/3 complex, binds PIP2. Present in the cleavage furrow in Tetrahymena, and required for cell division  Haugwitz et al, 1994; Balasubramanian, et al, 1994; Edamatsu et al, 1992.
ADF/Cofilin Binds and severs actin filaments possibly required for disassembling the contractile ring. Gunsalus et al, 1995;
IQGAP Required for the later stages of cytokinesis Adachi et al, 1997
AIP1 Works with cofilin in depolymerisation of actin during cytokinesis Konzok et al, 1999
Anillin A bundling protein, also present in the ring canals of Drosophila embryos Giansanti, et al, 1999; Field et al 1995
30kDa A bundling protein Furukawa & Fechheimer, 1994
Radixin Binds membranes and actin filaments.  This is important since a complete ring is not always necessary for the contractile ring to contract. Sarto et al, 1991
Talin Enriched in the cleavage furrow, possibly stitches the cleavage furrow to the membrane together with the similar protein radixin Sanger et al, 1994
Table 1 Actin Binding Proteins required for cytokinesis.

 

Actin-binding Protein Function Reference
a-actinin A bundling protein Furukawa & Fechheimer, 1994
34kDa A bundling protein from (Dictyostelium) Rivero et al, 1996
Villin Forms microvilli bundles and severs actin filaments Ca2+ sensitive. Franck et al, 1990
Gelsolin No suggestion of concentration in furrow, Gelsolin null mice are viable.
Table 2 Actin Binding Proteins that are not required for cytokinesis.

There are a few inconsistencies between various cell types as to the actual requirements of some ABPs for cytokinesis, for example Dictyostelium can apparently do without a-actinin for cytokinesis (Furukawa & Fechheimer, 1994), whereas it is present in the cleavage furrow of other cell types (Fujiwara et al, 1978) where is thought to be required.

The Rappaport Rules:  Where the cleavage furrow falls.

Classic experiments by Ray Rappaport established that the position of cleavage furrow formation was determined by the presence of sets of inter-digitating microtubules (Figure 1).  More recent experiments have confirmed this basic tenant (Cao & Wang, 1996) and details of the mechanisms by which signals are send by the spindle microtubules and received by the nascent contractile ring are slowly becoming more clear. The mid-zone not only establishes the position of the cleavage furrow but in some cells at least its continuous presence is require for the completion of cytokinesis (Wheatley & Wang 1996).

Figure 1 The Rappaport Rules1. A glass needle or bead was used to create a hole in a cell that was about to divide. 2. A cleavage furrow appeared between the separated chromosome masses as usual but the cell did not separate because of its shape. 3. At the subsequent round of division spindle poles were created at the two chromosome sets but an addition “spindle” was created by the interaction of the back to back astral microtubules.  4. This extra spindle now dictates the formation of an extra cleavage furrow.  Note that this results in four cells as would have arisen without the glass rod intervention. How the spindle pole or anti-parallel microtubule arrays dictate the cleavage furrow origin is not clear at the moment but some possible candidate signalling molecules are identified in table 3 (below).

The Nature of The Mid-body Signal, and the Recipient Molecules

The Rappaport rules clearly demonstrate that the inter-digitating microtubule arrays seem to determine the position of the cleavage furrow but the mechanism for this determination remain elusive (Cao & Wang, 1996).  The cleavage furrow can form without the presence of myosin II ruling myosin II out as being primarily involved. A number of signalling molecules are known to be associated with the mid-body and so are candidates for this elusive function. Some of these are tabulated in table 3 below.

Protein  Function References
Aurora kinase Forms a complex with INCENP and mitotic kinesin in the spindle and is required for cytokinesis.  Bischoff et al, 1998; Kaitna et al, 2000; Severson et al, 2000; Adams et al, 2000; Terada et al, 1998;
Citron kinase Rho-dependent kinase Madaule et al, 1995
CYK-4 A formin homology protein and a Rho GAP required for cytokinesis Swan et al, 1998; Jantsch-Plunger et al, 2001
ERK/MKK Shapiro et al, 1998
MgcRacGAP Binds MTs  Hirose et al, 2001
Plk Polo-like kinases  Golsteyn et al, 1995
INCENP Binds Aurora kinase and targets it to centrosomes and the spindle. Eckley et al, 1997; Kaitna et al, 2000; Adams et al, 2000.
PRC1 A homolog of yeast spindle elongation factor Ase1p Jiang et al, 1998; 
p34cdc2 Phosphorylates myosin II light chain and caldesmon at cytokinesis. Satterwhite et al, 1992; Mak et al, 1991
Table 3   Candidates for the Primary Mid-Body Signal?

The Rho pathway and Cytokinesis (Cyk-1, MgcRacGAP, Citron kinase)

RhoA is required for cortical retraction (step from 6 to 1 in figure 2 below) that takes place when cells round up prior to cytokinesis (Maddox & Burrdige, 2003). Many reports implicate Rho in cytokinesis. Rho has been found to localized to the cleavage furrow (Takaishi et al, 1995)  regulating cortical activity during cytokinesis (O'Connel et al, 1999) and has a role in the organisation of the contractile ring in sand dollar eggs (Mabuchi et al, 1993).  Microinjection of the Clostridium botulinum C3 toxin (which inhibits Rho proteins see Cytoskeletal acting toxins), inhibits cytokinesis (Kishi et al, 1993). Dutartre et al, 1996 Rho GTPase CDC42Hs. Madaule et al, 1998)

INCENP and the Aurora Kinase Complex.

 The Inner Centromere Protein (INCENP) was identified first as being the antigen against which patients made auto-antibodies to.  These antigens were seen to locate to the centrosomes and subsequently to the midbody during mitosis (Cooke et al, 1987).  It seems that because the midbody remnant is sometimes discarded by both daughter cells after cytokinesis antibodies are made to components of this antigen rich particle.  Aurora kinases form a complex with INCENP (Adams et al, 2000; Kaitna et al, 2000), and the mitotic kinesin: ZEN-4 (a.k.a. CeMKLP1) (Severson et al, 2000).  It is proposed that the aurora kinases actually have two roles in the processes of mitosis and cytokinesis (Severson et al, 2000; Kaitna et al, 2000).  Aurora kinases are thought to mediate separation of the sister chromatids and to function later in cytokinesis by directing the assembly of the spindle with ZEN-4. ZEN-4 can bind to and bundle anti-parallel purified microtubules (Nislow et al, 1992). The role of aurora kinase in cytokinesis is late in the process and the cleavage furrow can form without it (Severson et al, 2000) but in its absence the cleavage furrow regresses, this is possibly due the failure to target ZEN-4 to the spindle which is required to organise the microtubule array which in turn are known to be required throughout the entire cytokinesis (Wheatley et al, 1996).  It is not likely therefore that aurora kinase is the signal from the spindle that directs cleavage furrow formation, but this still leaves INCENP?

Polo-like Kinases.

(Nigg et al, 1998)

 

From Maciver, S. K. (1996) BioEssays. 18, 179-182.

Figure 2.  The role of myosin II at all stages of cytokinesis.  1. As the cell rounds up at the onset of cytokinesis, myosin II filaments move from the depolymerizing stress fibres and cell-cell adhesion sites into the cortex (under the plasma membrane) of the rounding cell. Myosin II helps this process by the disassembly of the mini-thick filaments and the concomitant loosening of the stress fibre and increases the cortical tension by forming filaments within it. 2 The main function of myosin II is to contract within the the formed cleavage furrow to steadily reduce its diameter as the spindle recedes towards the poles. 3. On completion of cytokinesis, the cell is still attached to the substrate by focal adhesion rudiments through "retraction filaments". 4. The cell then pulls itself back towards the substrate using myosin II filaments, gathered at the junction of the cell body  to work with the polar microfilaments within the retraction fibres (barbed ends at the focal adhesion) drawing the cell body back to the substrate it is important that the filaments in the retraction filaments are polar, with the pointed ends all facing the cell body, the correct orientation for a productive interaction with myosin II. 5. Myosin II continues to spread the cell, and the stress fibres are re-established.  

 

The Role of Myosin II in the Assembly and Contraction of the Cleavage Furrow.  

Myosin II has been detected in the cleavage furrow of many different cell types since its first discovery in lymphocytes (Fujiwara & Pollard, 1976). A role of myosin II in the contraction of the furrow has been demonstrated by the microinjection of antibodies against myosin II that inhibit its action in starfish eggs that arrest contraction (Mabuchi & Okuno, 1977), and by myosin II gene knockout experiments (Knecht & Loomis, 1987; deLozanne & Spudich, 1987). Myosin II is present as bi-polar mini-filaments within the cleavage furrow (Maupin & Pollard, 1986) the assembly and the contractile activity of these filaments is regulated by phosphorylation. In Dictyostelium, about 70 myosin monomers form each filament (Clarke & Spudich, 1974). Using GFP tagged point mutant myosin II heavy chains it was found that the phosphorylation sites that regulate Dictyostelium thick filament assembly are three threonine residues (T1823, T1833 & T2029) (Sabry et al, 1997).  This finding correlates with the behaviour of myosin II filaments in vitro under phosphorylation control (Kuczmarski & Spudich 1980).  The assembly of myosin-II filaments seemed to be prerequisite for their incorporation into the cleavage furrow. It is known that myosin II can locate to the furrow without motor function (Yumura & Uyeda 1997; Zang & Spudich, 1998)), suggesting that the filaments do not row themselves into place.  This then begs the question how do myosin II filaments accumulate in the furrow? A study to find a region of the myosin II molecule responsible for targeting it to the furrow concluded that there was no such region (Shu et al, 1999) and the myosin II carrying activity or mechanism remains at large.

Once within the cleavage furrow by this uncertain mechanism, however, the contractile activity of the bi-polar filaments is regulated by phosphorylation of the light chains, and there is evidence to suggest that myosin II filaments gather at the presumptive furrow even before any contractile activity is present as immunofluorescence indicates that the filaments exist at the site before the site can be distinguished morphologically (Fujiwara & Pollard, 1976; Mabuchi, 1994).  Many kinases phosphorylate myosin light chains some are inhibitory and other activate contraction.  Satterwhite et al, 1992).  Phosphorylation at serine 19 of the regulatory light chain (MRLC) of myosin II which increases contractile activity has been studied using a phospho-specific antibody (Matsumura et al, 1998) (see below).  This study with NRK epithelial cells indicates that the myosin II bipolar filaments are phosphorylated on serine 19 as the contractile ring forms.

 

Ca2+ /Calmodulin, Cytokinesis and Myosin

It has been known for some time that calcium signalling was vitally important to some cell types.  The injection of calcium buffers into Xenopus eggs inhibits cytokinesis (Miller et al, 1993) and waves of calcium have been recorded at the leading edge of the cleavage furrow. Calmodulin too may be involved as its reduction (by anti-sense mRNA) inhibits cytokinesis (Liu et al, 1992). Ca2+Calmodulin Kinase II is known to phosphorylate Myosin V (Karcher et al, 2001; Cheney & Rodriguez, 2001) causing it to release from its vesicle cargoes, but this has probably got more to do with a closing down of motile function of vesicle transport at the time of mitosis rather than being directly involved in cytokinesis.  Phosphorylation of MRLC by Ca2+/calmodulin-dependent myosin light chain kinase (MLCK) occurs on Ser19 mainly and is also diphosphorylated on Ser19 and Thr18 (Ikebe & Hartshorne, 1985), the diphospho MRLC is concentrated in the cleavage furrow (Iwasaki et al, 2001).

 

Membranes and Cytokinesis

In large cells at least, there is good reason to believe that membrane are inserted at the point of the cleavage furrow. Syntaxin mutants are known to inhibit cytokinesis in Caenorhabditis elegans (Jantsch-Plunger & Glotzer, 1999; Straight & Field, 2000) and sea urchin eggs (Conner & Wessels, 1999) and is required for cellularization of the Drosophila embryo (Burgess et al, 1997). Redistribution of phosphatidylethanolamine at the cleavage furrow (Emoto et al, 1996; Emoto & Umeda, 2001). Recently the lipid psychosine has been discovered to block cytokinesis and to dissociate mitosis from cytokinesis (reviewed Mitchison, 2001). Treated cells initiate cleavage furrows but these then fail.  Treated cells have dense polymerized clouds of actin and so it is thought that the actin that otherwise would form the cleavage furrow is diverted. 

 

Traction Mediated Cytokinesis - (Breaking up is never easy to do)

Some cell types seem reluctant to break the fine junction that connects cells after cytokinesis.  Studying the giant amoeba, Amoeba proteus Chalkey (Chalkey, 1935), described how after nuclear division the amoebae remained connected  and the cell crawled off in opposite directions until the cell tore itself apart.  This is very reminiscent of the situation in the much smaller soil amoeba  Dictyostelium discoideum when the single gene for myosin II heavy chain is deleted by homologous recombination de Lozanne & Spudich 1987), however Amoeba proteus expresses myosin II (Oh & Jeon, 1998).  Cell deficient in myosin II were found not to be capable of dividing in suspension yet were capable to do so when they were grown on a solid substrate.  The multinucleate cells were able to divide by each daughter cell crawling off in opposite directions.  This hypothesis was tested by culturing the myosin II deficient  Dictyostelium amoeba on non-adhesive surface, as expected, the cells could not divide as they could not develop sufficient traction on the surface to tear the cells in half (Zang et al, 1997).  A similar situation has also been recorded in vertebrate cells where after cytokinesis the cell remained connected by a narrow cytoplasmic bridge which was broken as the cells moved off (Mullins & Biesele, 1977).  In order to differentiate myosin II dependent cytokinesis from traction mediated (myosin II independent) cytokinesis, Zang and colleagues (Zang et al, 1997) have described the former (Myosin II dependent) as cytokinesis A and the latter (myosin II independent) cytokinesis B.  Recently (Biron et al, 2001), a bizarre phenomenon has been reported in Entamoeba where the final stage of cytokinesis is assisted by neighbouring ('midwife') amoeba.  These cells are recruited by a chemoattractant liberated by the amoeba in labour!  What the chemoattractant is and how the midwife cells succeed in separation of the daughter amoeba is presently unknown but a similar process has been seen in Dictyostelium (Biron et al, 2001).  A similar situation is now thought to occur in Dictyostelium amoebae (Insall et al, 2001)

Rotokinesis - A connected phenemenon?  Mutants of the ciliate Tetrahymena lacking kinesin-II are incapable of swimming as they do not form cilia,  These mutant ciliates were found not to be able to complete cytokinesis.  It is assumed that these ciliates normally complete cytokinesis by tearing themselves apart by swimming in opposite directions (Brown et al, 1999).

Figure 4.  Traction Mediated Cytokinesis. A.  A bi-nucleate cell produced through a failure of cytokinesis proper. B. Soon after, the cell polarizes and attempts to crawl in two opposite directions. C. This is accomplished and the cell rips its self in two. Cells or parts of cells do not normally tear off in this way so there may be some specific mechanism at work here possibly involving the activation of membrane fusion machinery. Consistent with this view is the fact that syntaxin mutant are deficient in the final stages of cytokinesis (Jantsch-Plunger & Glotzer, 1999). Syntaxin is a component of the membrane fusion machinery.. 

Cytokinesis Links

On this website:-

Centrosomes Mitosis/Meiosis
Kinetochores  Cytokinesis & Cancer
Asymmetric cytokinesis  

External links:-

The Cytokinesis Mafia
Bill Earnshaw's Lab ICMB Edinburgh

References:-

Adachi, H., Takahashi, Y., Hasebe, T., Shirouzu, M., Yokoyama, S. & Sutoh, K. (1997) Dictyostelium IQGAP-related protein specifically involved in the completion of cytokinesis. J.Cell Biol. 137, 891-898.

Adams, R. R., Wheatley, S. P., Gouldsworthy, A. M., Kandeis-Lewis, S. E., Carmena, M., Smythe, C., Gerloff, D. L. & Earnshaw, W. C. (2000) INCENP binds the Aurora-related kinase AIRK2 and is required to target it to chromosomes, the central spindle and cleavage furrow. Curr.Biol. 10, 1075-1078.

Andreassen, P. R., Palmer, D. K., Wener, M. H. & Margolis, R. L. (1991) Telophase disc: a new mammalian mitotic organelle that bisects telophase cells with a possible function in cytokinesis. J. Cell Sci. 99, 523-534.

Balasubramanian, M. K., Hirani, B. R., Burke, J. D. & Gould, K. L. (1994) The Schizosaccharomyces-pombe cdc3+ gene encodes a profilin essential for cytokinesis, Journal Of Cell Biology. 125, 1289-1301.

Balasubramanian, M. K., McCollum, D. & Surana, U. (2000) Tying the knot: linking cytokinesis to the nuclear cycle., J.Cell Sci. 113, 1503-1513.

Biron, D., Libros, P., Sagi, D., Mirelman, D. & Moses, E. (2001) 'Midwives' assist dividing amoebae., Nature. 410, 430.

Bischoff, J.R., Anderson, L., Zhu, Y., Mossie, K., Ng, L., Souza, B., Schryver, B., Flanagan, P., Clairvoyant, F., Ginter, C. Chan, C.S, Novotny, M., Slamon, D.J., & Plowman, G.D. (1998). EMBO J. 17, 3052-3065.

Brown, J.M., Hardin, C. & Gaertig, J. (1999). Rotokinesis, a novel phenomenon of cell locomotion-assisted cytokinesis in the ciliate Tetrahymena thermophila. Cell Biol. Int. 23, 841-848.

Burgess, R.W., Deitcher, D.L., & Schwartz, T.L. (1997). The synaptic protein syntaxin 1 is required for cellularization of Drosophila embryos. J.Cell Biol. 138, 861-875.

Burton, K. & Taylor, D. L. (1997) Traction forces of cytokinesis measured with optically modified elastic substratum. Nature. 385, 450-454.

Bowerman, B. & Severson, A. F. (1999) Cell division: plant-like properties of animal cell cytokinesis. Current Biology. 9, R658-R660.

Cao, L.-g. & Wang, Y.-L. (1990) Mechanism of the formation of contractile ring in dividing animal cells. I Recruitment of preexisting actin filaments into the cleavage furrow., J.Cell Biol. 110, 1089-1095.

Cao, L.-g. & Wang, Y.-L. (1990) Mechanism of the formation of contractile ring in dividing animal cells. II Cortical movement of microinjected actin filaments., J.Cell Biol. 111, 1905-1911.

Cao, L.-G. & Wang, Y.-L. (1996) Signals from the spindle midzone are required for the stimulation of cytokinesis in cultured epithelial cells, Mol.Biol.Cell. 7, 225-232.

Chang, F., Drubin, D. & Nurse, P. (1997) cdc12p, a protein required for cytokinesis in fission yeast, is a component of the cell division ring and interacts with profilin., J.Cell Biol. 137, 169-182.

Chalkey, H.W. (1935). The mechanism of cytoplasmic fission in Amoeba proteus. Protoplasma 24, 607-621.

Chalkey, H.W. (1951). Control of fission in Amoeba proteus as related to the mechanism of cell division. Ann.N.Y. Acad.Sci. 51, 1303-1310.

Cheney, R. E. & Rodriguez, O. C. (2001) A switch to release the motor, Science. 293, 1263-1264.

Cheng, A., Dean, N. M. & Honkanen, R. E. (2000) Serine/threonine protein phosphatase type1g1 is required for the completion of cytokinesis in human A549 lung carcinoma cells., J.Biol.Chem. 275, 1846-1854.

Conner, S.D. & Wessel, G.M. (1999). Syntaxin is required for cell division Mol.Biol.Cell 10, 2735-2743.

Cooke, C.A., Heck, M.M., Earnshaw, W.C. (1987). The inner centromere protein (INCENP) antigens: movement from inner centromere to midbody during cytokinesis. J.Cell Biol. 105, 2053-2067.

de Hostos, E. L., Rehfuess, C., Bradtke, B., Waddell, D. R., Albrecht, R., Murphy, J. & Gerisch, G. (1993) Dictyostelium mutants lacking the cytoskeletal protein coronin are defective in cytokinesis and cell motility, J. Cell Biol. 120, 163-173.

de Lozanne, A. & Spudich, J.A. (1987). Disruption of the Dictyostelium myosin heavy-chain gene by homologous recombination. Science 236, 1086-1091.

Dumontier, M., Hocht, P., Mintert, U. & Faix, J. (2000) Rac1 GTPases control filopodia formation, cell motility, endocytosis, cytokinesis and development in Dictyostelium., J.Cell Sci. 113, 2253-2265.

Dutartre, H., Davoust, J., Gorvel, J.-P. & Chavrier, P. (1996) Cytokinesis arrest and redistribution of actin-cytoskeleton regulatory components in cells expressing the Rho GTPase CDC42Hs, J. Cell Sci. 109, 367-377.

Eckley, D. M., Ainsztein, A. M., Mackey, A. M., Goldberg, I. & Earnshaw, W. C. (1997) Chromosomal proteins and cytokinesis: Patterns of cleavage furrow formation and inner centromere protein positioning in mitotic heterokaryons and mid-anaphase cells, J.Cell Biol. 136, 1169-1183.

Edamatsu, M., Hirono, M. & Watanabe, Y. (1992) Tetrahymena profilin is localized in the division furrow, J. Biochemistry. 112, 637-642.

Emoto, K., Kobayashi, T., Yamaji, A., Aizawa, H., Yahara, I., Inoue, K. & Umeda, M. (1996) Redistribution of phsophatidylethanolamine at the cleavage furrow of dividing cells during cytokinesis. PNAS 93, 12867-12872.

Emoto, K. & Umeda, M. (2001) Membrane lipid control of cytokinesis. Cell Structure & Function. 26, 659-665.

Eng, K., Naqvi, N. I., Wong, K. C. Y. & Balasubramanian, M. K. (1998) Rng2p, a protein required for cytokinesis in fission yeast, is a component of the actomyosin ring and the spindle pole body, Current Biol. 8, 611-621.

Faix, J., Steinmetz, M., Boves, H., Kammerer, R. A., Lottspeich, F., Mintert, U., Murphy, J., Stock, A., Aebi, U. & Gerisch, G. (1996) Cortexillins, major determinants of cell shape and size, are actin bundling proteins with a parallel coiled-coil tail, Cell. 86, 631-642.

Field, C. M. & Alberts, B. M. (1995) Anillin, a contractile ring protein that cycles from the nucleus to the cell cortex, J.Cell Biol. 131, 165-178.

Field, C., Li, R. & Oegema, K. (1999) Cytokinesis in eukaryotes: a mechanistic comparison, Curr.Op.Cell Biol. 11, 68-80.

Franck, Z., Footer, M. & Bretscher, A. (1990) Microinjection of villin into cultured cells induces rapid and long-lasting changes in cell morphology but does not inhibit cytokinesis, cell motility or membrane ruffling., J. Cell Biol. 111, 2475-2485.

Fujiwara, K. & Pollard, T. D. (1976) Fluorescent antibody localization of myosin in the cytoplasm, cleavage furrow and mitotic spindle of human cells., J.Cell Biol. 71, 848-875.

Fukui, Y. & Inoue, S. (1991). Cell division in Dictyostelium with special emphasis on actomyosin organization in cytokinesis. Cell Mot. Cytoskeleton 18, 41-54.

Fukui, Y., Engler, S., Inoue, S. & de Hostos, E. L. (1999) Architectural dynamics and gene replacement of coronin suggests its role in cytokinesis., Cell Motility Cytoskeleton. 42, 204-217.

Furukawa, R. & Fechheimer, M. (1994) Differential localization of a-actinin and the 30 kD actin-bundling protein in the cleavage furrow, phagocytic cup, and contractile vacuole of Dictyostelium discoideum, Cell Motility and Cytoskeleton. 29, 46-56.

Gerisch, G. & Weber, I. (2000) Cytokinesis without myosin II., Curr.Op.Cell Biol. 12, 126-132.

Giansanti, M. G., Bonaccorsi, S. & Gatti, M. (1999) The role of anillin in meiotic cytokinesis of Drosophila males., J.Cell Science. 112, 2323-2334.

Glotzer, M. (1997) Cytokinesis, Curr.Biol. 7, 274-276.

Golsteyn, R.M., Mundt, K.E., Fry, A.M., & Nigg, E.A. (1995) J.Cell Biol. 129, 1617-1628.

Gunsalus, K. C., Bonaccorsi, S., Williams, E., Verni, F., Gatti, M. & Goldberg, M. L. (1995) Mutations in twinstar, a Drosophila gene encoding a cofilin/ADF homologue, result in defects in centrosome migration and cytokinesis, J. Cell Biol. 131, 1243-1259.

Hales, K. G., Bi, E., Wu, J.-Q., Adam, J. C., Yu, I.-C. & Pringle, J. R. (1999) Cytokinesis: an emerging unified theory for eukaryotes?, Curr.Op.Cell Biol. 11, 717-725.

Haugwitz, M., Noegel, A. A., Karakesisoglou, J. & Schleicher, M. (1994) Dictyostelium amoebae that lack G-actin sequestering profilins show defects in F-actin content, cytokinesis and development., Cell. 79, 303-314.

Hiramoto, Y. (1975) Force exerted by the cleavage furrow of sea urchin eggs. Devel. Growth Diff. 17, 27-

Hirose, K., Kawashima, T., Iwamoto, I., Nosaka, T. & Kitamura, T. (2001) MgcRacGAP is involved in cytokinesis through associating with mitotic spindle and midbody., J.Biochem. 276, 5821-5828.

Insall, R. H., Muller-Taubenberger, A., Machesky, L. M., Kohler, J., Simmeth, E., Atkinson, S. J., Weber, I. & Gerisch, G. (2001) Dynamics of the Dictyostelium Arp2/3 complex in endocytosis, cytokinesis, and chemotaxis., Cell Motility Cytoskeleton. 50, 115-128.

Iwasaki, T., Murata-Hori, M., Ishitobi, S. & Hosoya, H. (2001) Diphosphorylated MRLC is required for organization of stress fibers in interphase cells and the contractile ring in dividing cells. Cell Structure & Function. 26, 677-683.

Jantsch-Plunger, V. & Glotzer, M. (1999) Depletion of syntaxins in the early Caenrhabditis elegans embryo reveals a role for membrane fusion events in cytokinesis., Curr. Biol. 9, 738-745.

Jantsch-Plunger, V., Gonczy, P., Romano, A., Schnabel, H., Hamill, D., Schnabel, R., Hyman, A.A. & Glotzer, M. (2000) J.Cell Biol. 149, 1391-1404.

Jensen, C.G. & Watson, M. (1999). Inhibition of cytokinesis by asbestos and synthetic fibres. Cell Biol. Int. 23(12), 829-840.

Jiang, W., Jimenez, G., Wells, N. J., Hope, T. J., Wahl, G. M., Hunter, T. & Fukunaga, R. (1998) PRC1: A human mitotic spindle-associated CDK substrate protein required for cytokinesis., Mol.Cell. 2, 877-885.

Kaitna, S., Mendoza, M., Jantsch-Plunger, V. & Glotzer, M. (2000) Incenp and an Auora-like kinase form a complex essential for chromosome segregation and efficient completion of cytokinesis., Curr.Biol. 10, 1172-1181.

Karcher, R. L., Roland, J. T., Zappacosta, F., Hudddleston, M. J., Annan, R. S., Carr, S. A. & Gelfand, V. I. (2001) Cell cycle regulation of myosin-V by Calcium/Calmodulin-dependent protein kinase II., Science. 293, 1317-1320.

Kawano, Y., Fukata, Y., Oshiro, N., Amano, M., Nakamura, T., Ito, M., Matsumura, F., Inagaki, M. & Kaibuchi, K. (1999) Phosphorylation of myosin-binding subunit (MBS) of myosin phosphatase by Rho-kinase during cell migration and cytokinesis., J.Cell Biol. 147, 1023-1037.

Kishi, K., Sasaki, T., Kuroda, S., Itoh, T. & Takai, Y. (1993) J.Cell Biol. 120, 1187-1195.

Knecht, D. A. & Loomis, W. F. (1987) Antisense RNA inactivation of myosin heavy chain gene expression in Dictyostelium discoideum., Science. 236, 1081-1085.

Konzok, A., Weber, I., Simmeth, E., Hacker, U., Maniak, M. & Muller-Taubenberger, A. (1999) DAip1, a Dictyostelium homologue of the yeast actin-interacting protein 1, is involved in endocytosis, cytokinesis, and motility., J.Cell Biol. 146, 453-464.

Kuczmarski, E.R. & Spudich, J.A. (1980). Regulation of myosin self-assembly: phosphorylation of Dictyostelium heavy chain inhibits formation of thick filaments. PNAS 77, 7292-7296.

Larochelle, D. A., Vithalani, K. K. & DeLozanne, A. (1996) A novel member of the rho family of small GTP-binding proteins is specifically required for cytokinesis, J.Cell Biol. 133, 1321-1329.

Lippincott, J. & Li, R. (1998) Sequential assembly of myosin II, an IQGAP-like protein, and filamentous actin to a ring structure involved in budding yeast cytokinesis, J.Cell Biol. 140, 355-366.

Liu, T., Williams, J.G., Clarke, M. (1992). Inducible expression of calmodulin antisense RNA in Dictyostelium cells inhibits the completion of cytokinesis. Mol.Biol.Cell 3, 1403-1413.

Mabuchi, I.& Okuno, M. (1977). The effect of myosin antibody on the division of starfish blastomeres. J.Cell Biol. 74, 251-263.

Mabuchi, I. (1994) Cleavage furrow: timing of emergence of contractile ring actin filaments and establishment of the contractile ring by filament bundling in sea urchin eggs, J. Cell Sci. 107, 1853-1862.

Mabuchi, I., Hamaguchi, Y., Fujimoto, H., Morii, N., Mishima, M. & Narumiya, S. (1993) A Rho-like protein is involved in the organization of the contractile ring in dividing sand dollar eggs. Zygote 1, 325-331.

Maciver, S. K. (1996) Myosin II function in non-muscle cells, BioEssays. 18, 179-182.

Madaule, P., Eda, M., Watanabe, N., Fujisawa, K., Matsuoka, T., Bito, H., Ishizaki, T., & Narumiya, S. (1998) Role of citron kinases as a target of the small GTPase rho in cytokinesis. Nature 394, 491-494.

Maddox, A. S. & Burridge, K. (2003) RhoA is required for cortical retraction and rigidity during mitotic cell rounding. J.Cell Biol. 160, 255-265.

Mak, A.S., Carpenter, M., Smillie, L.B., & Wang, J.H. (1991) Phosphorylation of caldesmon by p34cdc2 kinase. Identification of phosphorylation sites. J.Biol.Chem. 266, 19971-19975.

Matsumura, F., Ono, S., Yamakita, Y., Totsukawa, G. & Yamashiro, S. (1998) Specific localization of serine 19 phosphorylated myosin II during cell locomotion and mitosis of cultured cells., J.Cell Biol. 140, 119-129.

Maupin. P. & Pollard, T.D. (1986). Arrangement of actin filaments and myosin-like filaments in the contractile ring and of actin-like filaments in the mitotic spindle of dividing HeLa cells. J.Ultrastructure Mol. Struct.Res. 94, 92-103.

Megraw, T. L., Kao, L.-R. & Kaufman, T. C. (2001) Zygotic development without functional mitotic centrosomes., Curr.Biol. 11, 116-1120.

Miller, A. L., Fluick, R. A., McLaughlin, J. A. & Jaffe, L. F. (1993) Calcium buffer injections inhibit cytokinesis in Xenopus eggs, J. Cell Sci. 106, 523-534.

Mitchison, T. J. (2001) Psycosine, cytokinesis, and orphan receptors: Unexpected connections. J.Cell Biol. 153, F1-F3.

Mullins, J.M. & Biesele, J.J. (1977). Terminal phase of cytokinesis in D-98S cells. J.Cell Biol. 73, 672-684.

Nagaoka, R., Abe, H., Kusano, K. & Obinata, T. (1995) Concentration of cofilin, a small actin-binding protein, at the cleavage furrow during cytokinesis, Cell Motility And The Cytoskeleton. 30, 1-7.

Nagasaki, A., Hibi, M., Asano, Y. & Uyeda, T. Q. P. (2001) Genetic approaches to dissect the mechanisms of two distinct pathways of cell cycle-coupled cytokinesis in Dictyostelium. Cell Structure & Function. 26, 585-591.

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.

Nigg, E.A. (1998) Polo-like kinases: positive regulators of cell division from start to finnish. Curr.Op.Cell Biol. 10, 776-783.

Nislow, C., Lombillo, V.A., Kuriyama, R. & McIntosh, J.R. (1992). A plus-end-directed motor enzyme that moves antiparallel microtubules in vitro localizes to the interzone of mitotic spindles. Nature 359, 543-547.

Noegel, A. A., Rivero, F., Albrecht, R., Janssen, K.-P., Kohler, J., Parent, C. A. & Schleicher, M. (1999) Assessing the role of the ASP56/CAP homologue of Dictyostelium discoideum and the requirements for subcellular localization., J.Cell Sci. 112, 3195-3203.

Noguchi, T. & Mabuchi, I. (2000) Reorganization of actin cytoskeleton at the growing end of the cleavage furrow of Xenopus egg during cytokinesis., J.Cell.Sci. 114, 401-412.

O'Connel, C.B., Wheatley, S.P., Ahmed, S. & Wang, Y.L. (1999). The small GTP-binding protein Rho regulates cortical activites in culture cells during division. J.Cell Biol. 144, 305-313.

Oh, S. W. & Jeon, K. W. (1998) Characterization of myosin heavy chain and its gene in Amoeba proteus, J.Euk.Microbiol. 45, 600-605.

Perry, M.M., John, H.A., Thomas, N.S.T. (1971) Actin-like filaments in the cleavage furrow of newt eggs. Exp.Cell Res. 65, 249.

Pollard, T.D., Satterwhite, L., Cisek, L., Corden, J., Sato, M., & Maupin, P. (1990). Actin and myosin in relation to cytokinesis. In "Cytokinesis: Mechanisms of furrow formation during cell division." Ann.N.Y.Acad.Sci. 582, 120-130.

Rappaport, R. (1967). Cell division. Direct measurement of maximum tension exerted by furrow of echinoderm eggs. Science 156, 1241-1243.

Rappaport, R. (1986). Establishment of the mechanism of cytokinesis in animal cells. Int.Rev.Cytol. 105, 245-281.

Rivero, F., Furukawa, R., Noegel, A. A. & Fechheimer, M. (1996) Dictyostelium discoideum cells lacking teh 34,000-dalton actin binding protein can grow, locomote, and develop, but exhibit defects in regulation of cell structure and movement: A case of partial redundancy, J.Cell Biol. 135, 965-980.

Rivero, F., Furukawa, R., Fechheimer, M. & Noegel, A. A. (1999) Three actin cross-linking proteins, the 34 kDa actin bundling protein, a-actinin and gelation factor (ABP-120), have both unique and redundant roles in the growth and development of Dictyostelium., J.Cell Sci. 112, 2737-2751.

Robinson, D. N. & Spudich, J. A. (2000) Dynacortin, a genetic link between equatorial contractility and global shape control discovered by library complementation of a Dictyostelium discoideum cytokinesis mutant., J.Cell Biol. 150, 823-838.

Robinson, D. N., Cavet, G., Warrick, H. M. & Spudich, J. A. (2002) Quantitation of the distribution and flux of myosin-II during cytokinesis. BMC Cell Biology. 3, 1-13.

Sabry, J. H., Moores, S. L., Ryan, S., Zang, J.-H. & Spudich, J. A. (1997) Myosin heavy chain phosphorylation sites regulate myosin localization during cytokinesis in live cells., Mol. Biol.Cell. 8, 2605-2615.

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

Sarto, N., Yonemura, S., Obinata, T., Tsukita, S. & Tsukita, S. (1991) Radixin, a barbed end capping actin-modulating protein is concentrated at the cleavage furrow during cytokinesis, J. Cell Biol. 113, 321--330.

Satterwhite, L. S. & Pollard, T. D. (1992) Cytokinesis, Current Biol. 4, 43-52.

Satterwhite, L. S. , Lohka, M.J., Wilson, K.L., Scherson, T.Y., Cisek, L.J., Corden, J.L., & Pollard, T. D. (1992) Phosphorylation of myosin-II regulator light chain by cyclin-p34cdc2: a mechanism for the timing of cytokinesis. J.Cell Biol. 118, 595-605.

Saunders, W.S., Shuster, M., Huang, X., Gharaibeh, B., Enyenihi, A.H., Petersen, I., & Gollin, S.M. (2000). Chromosomal instability and cytoskeletal defects in oral cancer cells. PNAS 97, 303-308

Schroeder, T.E. (1968). Cytokinesis: filaments in the cleavage furrow. Exp.Cell Res. 53, 272.

Schroeder, T.E. (1972). Actin in dividing cells: contractile ring filaments bind heavy meromyosin. PNAS 70, 1688-1692.

Schroeder, T.E. (1976). Actin in dividing cells: Evidence for its role in cleavage but not mitosis. "Cell Motility". Cold Spring Harbor Conferences on Cell Proliferation. 3, 265-277

Severson, A. F., Hamill, D. R., Carter, J. C., Schumacher, J. & Bowerman, B. (2000) The Aurora-related kinase AIR-2 recruits ZEN-4/CeMKLP1 to the mitotic spindle at metaphase and is required for cytokinesis., Curr.Biol. 10, 1162-1171.

Shapiro, P.S., Vaisberg, E., Hunt, A.J., Tolwinski, N.S., Whalen, A.M., McIntosh, J.R., & Ahn, N.G. (1998) J.Cell Biol. 142, 1533-1545.

Shu, S., Lee, R.J., LeBlanc-Straceski, J.-M. & Uyeda, T.Q.P. (1999). Role of myosin II tail sequences in its function and localization at the cleavage furrow in Dictyostelium. J.Cell Sci. 112, 2195-2201.

Shuster, C. B. & Burgess, D. R. (1999) Parameters that specify the timing of cytokinesis, J.Cell Biol. 146, 981-992.

Smith, J.L., Silveira, L.A. & Spudich, J.A. (1996). Myosin light chain kinase (MLCK) gene disruption in Dictyostelium: a role for MLCK-A in cytokinesis and evidence for multiple MLCKs PNAS 93, 12321-12326

Stock, A., Steinmertz, M. O., Janmey, P. A., Aebi, U., Gerisch, G., Kammerer, R. A., Weber, I. & Faix, J. (1999) Domain analysis of cortexillin I: actin bundling, PIP2-binding and the rescue of cytokinesis., EMBO. 18, 5274-5284.

Straight, A. F. & Field, C. M. (2000) Microtubules, membranes and cytokinesis, Curr.Biol. 10, R760-R770.

Suetsuga, S., Miki, H. & Takenawa, T. (1999) Distinct roles of profilin in cell morphogenesis changes: microspikes, membrane ruffles, stress fibers, and cytokinesis., FEBS. tba.

Swan, K.A., Severson, AF., Carter, J.C., Martin, P.R., Schabel, H., Schnabel, R. & Bowerman, B. (1998). Cyk-1: a C.elegans FH gene required for a late step in embryonic cytokinesis. J.Cell Sci. 111, 2017-2027.

Tatsumoto, T., Xie, X., Blumenthal, R., Okamoto, I. & Miki, T. (1999) Human ECT2 is an exchange factor for Rho GTPases, phosphorylated in G2/M phases, and involved in cytokinesis., J.Cell Biol. 147, 921-927.

Takaishi, K., Sasaki, T., Kameyama, T., Tsukita, S. & Takai,Y. (1995) Oncogene 11, 39-48.

Terada, Y., Tatsuka, M., Suzuki, F., Yasuda, Y., Fujita, S., & Otsu, M. (1998) Aim-1: a mammalian midbody-associated protein required for cytokinesis. EMBO J. 17, 667-676.

Theriot, J. A. & Satterwhite, L. L. (1997) New wrinkles in cytokinesis, Nature. 385, 388-389.

Tosuji, H., Mabuchi, I., Fusetani, N. & Nakazawa, T. (1992) Calyculin A induces contractile ring-like apparatus formation and condensation of chromosomes in unfertilized sea urchin eggs, Cell Biol. 89, 10613-10617.

Tuxworth, R. I., Cheetham, J. L., Machesky, L. M., Spiegelmann, G. B., Weeks, G. & Insall, R. H. (1997) Dictyostelium RasG is required for normal motility and cytokinesis, but not growth, J.Cell Biol. 138, 605-614.

Walker, G. R., Shuster, C. B. & Burgess, D. R. (1997) Microtubule-entrained kinase activites associated with the cortical cytoskeleton during cytokinesis, J.Cell Sci. 110, 1373-1386.

Weber, I., Gerisch, G., Heizer, C., Murphy, J., Badelt, K., Stock, A., Schwartz, J.-M. & Faix, J. (1999) Cytokinesis mediated through the recruitment of cortexillins into the cleavage furrow, EMBO J. 18, 586-954.

Weber, I. (2001) On the mechanism of cleavage furrow ingression in Dictyostelium. Cell Structure & Function. 26, 577-584.

Wheatley, S. P. & Wang, Y.-l. (1996) Midzone microtubule bundles are continuously required for cytokinesis in cultured epithelial cells., J.Cell Biol. 135, 981-989.

Wheatley, S. P., Hinchcliffe, E. H., Glotzer, M., Hyman, A. A., Sluder, G. & Wang, Y.-L. (1997) CDK1 inactivation regulates anaphase spindle dynamics and cytokinesis in vivo., J.Cell Biol. 138, 385-393.

Wheatley, S. P. (1999) Updates on the mechanics and regulation of cytokinesis in animal cells., Cell Biol.Internat. 23, 797-803.

Win, T. Z., Gachet, Y., Mulvihill, D. P., May, K. M. & Hyams, J. S. (2000) Two type V myosins with non-overlapping functions in the fission yeast Schizosaccharomyces pombe: Myo52 is concerned with growth polarity and cytokinesis, Myo51 is a component of the cytokinetic actin ring., J.Cell Sci. 114, 69-79.

Wolf, W. A., Chew, T.-L. & Chisholm, R. L. (1999) Regulation of cytokinesis, Cell Mol. Life Sci. 55, 108-120.

Yamakita, Y., Yamashiro, S. and Matsumura, F. (1994). In vivo phosphorylation of regulatory light chain of myosin II during mitosis of cultured cells. J.Cell Biol.124, 129-137.

Yumura, S. & Uyeda, T.Q.P. (1997). Transport of myosin II to the equatorial region without its own motor activity in mitotic Dictyostelium cells. Mol. Biol. Cell 8, 2089-2099.

Yumura, S. & Fukui, Y. (1998) Spatiotemporal dynamics of actin concentration during cytokinesis and locomotion in Dictyostelium., J.Cell Sci. 111, 2097-2108.

Zang, J.-H., Cavet, G., Sabry, J.H., Wagner, P., Moores, S.L. & Spudich, J.A. (1997). On the role of myosin-II in cytokinesis: division of Dictyostelium cells under adhesive and non-adhesive conditions. Mol.Biol.Cell 8, 2617-2629.

Zang, J.-H. & Spudich, J.A. (1998) Myosin II localization during cytokinesis occurs by a mechanism that does not require its motor domain. PNAS 95, 13652-13657.

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