Novel cytokinetic ring proteins, the Ste20 family kinase GCK-1 (germinal center kinase-1) and its heterodimeric cofactor CCM-3 (cerebral cavernous malformations-3), close a negative feedback loop involving the RhoA GAP RGA-3/4, RhoA, and its cytoskeletal effector anillin to limit actomyosin contractility in cytokinesis and during polarization of the Caenorhabditis elegans zygote.
Actomyosin-driven cortical contractility is a hallmark of many biological processes. While most attention has been given to the positive regulation of contractility, it is becoming increasingly appreciated that contractility is also limited by negative regulation and mechanical brakes. The cytokinetic ring is an actomyosin contractile structure whose assembly and constriction are activated by the small GTPase RhoA. Here we describe the role of two novel cytokinetic ring components GCK-1 and CCM-3 in inhibiting contractility in the cytokinetic ring. GCK-1 and CCM-3 co-localize with essential cytokinetic ring proteins such as active RhoA, the scaffold protein anillin and non-muscle myosin II (NMM-II) during anaphase. GCK-1 and CCM-3 are interdependent for their localization and require active RhoA and anillin but not NMM-II for their recruitment to the cytokinetic furrow. Partial depletion of either GCK-1 or CCM-3 leads to an increase of active RhoA, anillin and NMM-II in the cytokinetic furrow and increased rates of furrow ingression. Furthermore, GCK-1 and CCM-3 localize to actomyosin foci during pulsed contractility of the cortical cytoskeleton during zygote polarization. Depletion of GCK-1 or CCM-3 leads to an increase in both cortical contractility and baseline active RhoA levels. Together, our findings suggest that GCK-1 and CCM-3 limit contractility during zygote polarization and
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