MgcRacGAP regulates cortical activity through RhoA during cytokinesis.
Although Rho GTPases regulate multiple cellular events, their role in cell division is still obscure. Here we show that expression of a GTPase-activating protein (GAP)-deficient mutant (R386A) of the Rho regulator MgcRacGAP induces abnormal cortical activity during cytokinesis in U2OS cells. Multiple large blebs were observed in cells expressing MgcRacGAP R386A from the onset of anaphase to the late stage of cell division. When mitotic blebbing was excessive, cytokinesis was inhibited, and cells with micronuclei were generated. It has been reported that blebbing is caused by abnormal cortical activity. The MgcRacGAP R386A-induced abnormal cortical activity was inhibited by the dominant negative form of RhoA, but not Rac1 or Cdc42. Moreover, expression of constitutively active RhoA also induced drastic cortical activity during cytokinesis. Unlike apoptotic blebbing, MgcRacGAP R386A-induced blebbing was not inhibited by the ROCK inhibitor Y-27632, suggesting that MgcRacGAP regulates cortical activity during cytokinesis through a novel signaling pathway. We propose that MgcRacGAP plays a pivotal role in cytokinesis by regulating cortical movement through RhoA.
Lee
Jae-Seon
JS
Molecular Tumor Biology Section, Basic Research Laboratory, National Cancer Institute, Bethesda, MD 20892-4255, USA. jaeslee@snu.ac.kr
Kamijo
Keiju
K
Ohara
Naoya
N
Kitamura
Toshio
T
Miki
Toru
T
D002455:Cell Division / Q000235:genetics; D045744:Cell Line, Tumor; D022081:Cell Surface Extensions / Q000235:genetics / Q000378:metabolism; D003595:Cytoplasmic Streaming / Q000235:genetics; D003599:Cytoskeleton / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020690:GTPase-Activating Proteins / Q000172:deficiency* / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009154:Mutation / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
D004791:Enzyme Inhibitors; D020690:GTPase-Activating Proteins; D047908:Intracellular Signaling Peptides and Proteins; C115995:mgcRacGAP; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein