During cytokinesis of animal cells, the mitotic spindle plays at least two roles. Initially, the spindle positions the contractile ring. Subsequently, the central spindle, which is composed of microtubule bundles that form during anaphase, promotes a late step in cytokinesis. How the central spindle assembles and functions in cytokinesis is poorly understood. The cyk-4 gene has been identified by genetic analysis in Caenorhabditis elegans. Embryos from cyk-4(t1689ts) mutant hermaphrodites initiate, but fail to complete, cytokinesis. These embryos also fail to assemble the central spindle. We show that the cyk-4 gene encodes a GTPase activating protein (GAP) for Rho family GTPases. CYK-4 activates GTP hydrolysis by RhoA, Rac1, and Cdc42 in vitro. RNA-mediated interference of RhoA, Rac1, and Cdc42 indicates that only RhoA is essential for cytokinesis and, thus, RhoA is the likely target of CYK-4 GAP activity for cytokinesis. CYK-4 and a CYK-4:GFP fusion protein localize to the central spindle and persist at cell division remnants. CYK-4 localization is dependent on the kinesin-like protein ZEN-4/CeMKLP1 and vice versa. These data suggest that CYK-4 and ZEN-4/CeMKLP1 cooperate in central spindle assembly. Central spindle localization of CYK-4 could accelerate GTP hydrolysis by RhoA, thereby allowing contractile ring disassembly and completion of cytokinesis.
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26 June 2000
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June 26 2000
Cyk-4: A Rho Family Gtpase Activating Protein (Gap) Required for Central Spindle Formation and Cytokinesis
Verena Jantsch-Plunger,
Verena Jantsch-Plunger
aResearch Institute of Molecular Pathology, A-1030 Vienna, Austria
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Pierre Gönczy,
Pierre Gönczy
bEuropean Molecular Biology Lab, Heidelberg D-69117, Germany
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Alper Romano,
Alper Romano
aResearch Institute of Molecular Pathology, A-1030 Vienna, Austria
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Heinke Schnabel,
Heinke Schnabel
cTechnical University Braunschweig, D-38106, Braunschweig, Germany
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Danielle Hamill,
Danielle Hamill
dUniversity of Oregon, Beaverton, Oregon 97403
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Ralf Schnabel,
Ralf Schnabel
cTechnical University Braunschweig, D-38106, Braunschweig, Germany
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Anthony A. Hyman,
Anthony A. Hyman
bEuropean Molecular Biology Lab, Heidelberg D-69117, Germany
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Michael Glotzer
Michael Glotzer
aResearch Institute of Molecular Pathology, A-1030 Vienna, Austria
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Verena Jantsch-Plunger
aResearch Institute of Molecular Pathology, A-1030 Vienna, Austria
Pierre Gönczy
bEuropean Molecular Biology Lab, Heidelberg D-69117, Germany
Alper Romano
aResearch Institute of Molecular Pathology, A-1030 Vienna, Austria
Heinke Schnabel
cTechnical University Braunschweig, D-38106, Braunschweig, Germany
Danielle Hamill
dUniversity of Oregon, Beaverton, Oregon 97403
Ralf Schnabel
cTechnical University Braunschweig, D-38106, Braunschweig, Germany
Anthony A. Hyman
bEuropean Molecular Biology Lab, Heidelberg D-69117, Germany
Michael Glotzer
aResearch Institute of Molecular Pathology, A-1030 Vienna, Austria
Abbreviations used in this paper: GAP, GTPase activating protein; GEF, guanine nucleotide exchange factor; GFP, green fluorescent protein; RNAi, RNA-mediated interference; ts, temperature-sensitive.
Received:
March 27 2000
Revision Requested:
May 12 2000
Accepted:
May 16 2000
Online ISSN: 1540-8140
Print ISSN: 0021-9525
© 2000 The Rockefeller University Press
2000
The Rockefeller University Press
J Cell Biol (2000) 149 (7): 1391–1404.
Article history
Received:
March 27 2000
Revision Requested:
May 12 2000
Accepted:
May 16 2000
Connected Content
Citation
Verena Jantsch-Plunger, Pierre Gönczy, Alper Romano, Heinke Schnabel, Danielle Hamill, Ralf Schnabel, Anthony A. Hyman, Michael Glotzer; Cyk-4: A Rho Family Gtpase Activating Protein (Gap) Required for Central Spindle Formation and Cytokinesis. J Cell Biol 26 June 2000; 149 (7): 1391–1404. doi: https://doi.org/10.1083/jcb.149.7.1391
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