Opposing roles of p190RhoGAP and Ect2 RhoGEF in regulating  cytokinesis.
Evidence suggests that p190RhoGAP (p190), a GTPase activating protein (GAP) specific for Rho, plays a role in cytokinesis. First, ectopic expression of p190 induces a multinucleated cellular phenotype. Second, endogenous p190 localizes to the cleavage furrow of dividing cells. Lastly, its levels are reduced in late mitosis by ubiquitin-mediated proteasomal degradation, consistent with the idea that low levels of p190 and high levels of active Rho are required for completion of cytokinesis. As with p190, RhoA and the RhoGEF, ECT2, have been localized to the cleavage furrow. These findings raise the question of whether p190 and ECT2 cooperate antagonistically to regulate the activity of Rho and contraction of the actomyosin ring during cytokinesis. Here we demonstrate ECT2 can, in a dose-dependent manner, reduce multinucleation induced by p190. Furthermore, endogenous p190 and ECT2 colocalize at the cleavage furrow of dividing cells and stably associate with one another in co-immunoprecipitation assays. Functional and physical interactions between p190 and ECT2 are reflected in the levels of Rho activity, as assessed by Rho pull-down assays. Together, these results suggest that co-regulation of Rho activity by p190RhoGAP and ECT2 in the cleavage furrow determines whether cells properly complete cytokinesis.
Mikawa
Masahito
M
Department of Microbiology and Cancer Center, University of Virginia Health System, Charlottesville, Virginia 22908, USA.
Su
Ling
L
Parsons
Sarah J
SJ
D002453:Cell Cycle; D048749:Cytokinesis; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D064067:Rho Guanine Nucleotide Exchange Factors; D020741:rho GTP-Binding Proteins / Q000378:metabolism
C074560:ARHGAP35 protein, human; C489850:ECT2 protein, human; D020662:Guanine Nucleotide Exchange Factors; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D064067:Rho Guanine Nucleotide Exchange Factors; D020741:rho GTP-Binding Proteins