Control of Rho family GTPases during cytokinesis
Final Report Abstract
Cytokinesis completes mitosis, dividing a single cell into two. To ensure that each daughter cell receives a single genomic complement, the cytokinetic furrow assembles in response to signals from the anaphase spindle, coupling cytokinesis to chromosome segregation. The anaphase spindle controls cortical remodeling by regulating the activity of members of the small Rho GTPases family, which in turn control the structure and contractility of the actin-rich cortex. Signaling by the anaphase spindle generates a narrow equatorial zone of active RhoA that directs the cortical accumulation of contractile ring components. In addition to the activation of RhoA, recent work in my sponsor laboratory has shown that downregulation of the small GTPase Rac is also essential for furrow ingression during cytokinesis. To understand how the anaphase spindle coordinately regulates RhoA and Rac, my first aim was to develop probes to monitor how RhoA and Rac spatiotemporal activity is controlled in the Caenorhabditis elegans embryo. Since several attempts to generate in vivo probes for active RhoA and Rac in C. elegans were unsuccessful and I focused my attention of my forth aim to study novel regulators that control RhoA activity. I identified RGA-3/4 in C. elegans and ARHGAP11a in HeLa cells as the critical RhoAGAPs that restrict RhoA activity temporally during mitosis and cytokinesis. My work shows further that the spatial patterning of RhoA activity during anaphase is largely independent of the RhoAGAP but depends on the centrosomal asters.
Publications
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“Affinity Purification of Protein Complexes in C. elegans.” Methods Cell Biol. 2011;106:289-322
E. Zanin, J. Dumont, R. Gassmann, I. Cheeseman, P. Maddox, S. Bahmanyar, A. Carvalho, S. Niessen, J. R. Yates III, K. Oegema and A. Desai
