PRC1 controls spindle polarization and recruitment of cytokinetic factors during monopolar cytokinesis.
The central spindle is a postanaphase array of microtubules that plays an essential role in organizing the signaling machinery for cytokinesis. The model by which the central spindle organizes the cytokinetic apparatus is premised on an antiparallel arrangement of microtubules, yet cells lacking spindle bipolarity are capable of generating a distal domain of ectopic furrowing when forced into mitotic exit. Because protein regulator of cytokinesis (PRC1) and kinesin family member 4A (KIF4A) are believed to play a principal role in organizing the antiparallel midzone array, we sought to clarify their roles in monopolar cytokinesis. Although both factors localized to the distal ends of microtubules during monopolar cytokinesis, depletion of PRC1 and KIF4A displayed different phenotypes. Cells depleted of PRC1 failed to form a polarized microtubule array or ectopic furrows following mitotic exit, and recruitment of Aurora B kinase, male germ cell Rac GTPase-activating protein, and RhoA to the cortex was impaired. In contrast, KIF4A depletion impaired neither polarization nor ectopic furrowing, but it did result in elongated spindles with a diffuse distribution of cytokinetic factors. Thus, even in the absence of spindle bipolarity, PRC1 appears to be essential for polarizing parallel microtubules and concentrating the factors responsible for contractile ring assembly, whereas KIF4A is required for limiting the length of anaphase microtubules.
Department of Biology, New Mexico State University, Las Cruces, NM 88003, USA.
Sanjay
S
Shrestha
Lori Jo
LJ
Wilmeth
Jarrett
J
Eyer
Charles B
CB
Shuster
D064107:Aurora Kinase B; D064127:Aurora Kinases; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors; D018797:Cell Cycle Proteins / Q000378:metabolism*; D016764:Cell Polarity / Q000502:physiology; D048749:Cytokinesis / Q000187:drug effects / Q000502:physiology*; D020690:GTPase-Activating Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D059705:Polar Bodies / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D018797:Cell Cycle Proteins; D020690:GTPase-Activating Proteins; C116662:PRC1 protein, human; D047428:Protein Kinase Inhibitors; C115995:mgcRacGAP; C066737:RHOA protein, human; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; C484228:KIF4A protein, human; D016547:Kinesins; D020742:rhoA GTP-Binding Protein