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Inhibition of Rac by the GAP Activity of Centralspindlin Is Essential for Cytokinesis
Open accessAbstract
During cytokinesis, the guanosine triphosphatase (GTPase) RhoA orchestrates contractile ring assembly and constriction. RhoA signaling is controlled by the central spindle, a set of microtubule bundles that forms between the separating chromosomes. Centralspindlin, a protein complex consisting of the kinesin-6 ZEN-4 and the Rho family GTPase activating protein (GAP) CYK-4, is required for central spindle assembly and cytokinesis in Caenorhabditis elegans . However, the importance of the CYK-4 GAP activity and whether it regulates RhoA remain unclear. We found that two separation-of-function mutations in the GAP domain of CYK-4 lead to cytokinesis defects that mimic centralspindlin loss of function. These defects could be rescued by depletion of the GTPase Rac or its effectors, but not by depletion of RhoA. Thus, inactivation of Rac by centralspindlin functions in parallel with RhoA activation to drive contractile ring constriction during cytokinesis.
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Cited by
Actin–microtubule crosstalk in cell biology
Dogterom, M., & Koenderink, G. H. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0067-1 · Cited by 574
Rho and Ras GTPases in axon growth, guidance, and branching
Hall, A., & Lalli, G. (2010) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a001818 · Cited by 437
Humphries, J. D., Byron, A., Bass, M. D., Craig, S. E., Pinney, J. W., Knight, D., & Humphries, M. J. (2009) · Science Signaling · doi:10.1126/scisignal.2000396 · Cited by 404
Cytokinetic Abscission: Molecular Mechanisms and Temporal Control
Mierzwa, B., & Gerlich, D. W. (2014) · Developmental Cell · doi:10.1016/j.devcel.2014.11.006 · Cited by 288
Centralspindlin: at the heart of cytokinesis
White, E. A., & Glotzer, M. (2012) · Cytoskeleton · doi:10.1002/cm.21065 · Cited by 168
Metadata
- Authors
- Canman, J. C., Lewellyn, L., Laband, K., Smerdon, S. J., Desai, A., Bowerman, B., & Oegema, K.
- Venue
- Science
- Published
- 2008-12-05
- Volume
- 322
- Issue
- 5907
- Pages
- 1543-1546
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1967153481
- Cited by
- 175
- References
- 0
- FWCI
- 4.34
- Type
- journal article
- Language
- en
- Open access
- green
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- Canman, J. C., Lewellyn, L., Laband, K., Smerdon, S. J., Desai, A., Bowerman, B., & Oegema, K. (2008). Inhibition of Rac by the GAP Activity of Centralspindlin Is Essential for Cytokinesis. Science. https://doi.org/10.1126/science.1163086
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