PT - JOURNAL ARTICLE AU - Kathryn Rehain Bell AU - Michael E. Werner AU - Anusha Doshi AU - Daniel B. Cortes AU - Adam Sattler AU - Thanh Vuong-Brender AU - Michel Labouesse AU - Amy Shaub Maddox TI - Novel cytokinetic ring components drive negative feedback in cortical contractility AID - 10.1101/633743 DP - 2020 Jan 01 TA - bioRxiv PG - 633743 4099 - http://biorxiv.org/content/early/2020/05/03/633743.short 4100 - http://biorxiv.org/content/early/2020/05/03/633743.full AB - Actomyosin cortical contractility drives many cell shape changes including cytokinetic furrowing. While positive regulation of contractility is well characterized, counterbalancing negative regulation and mechanical brakes are less well understood. The small GTPase RhoA is a central regulator, activating cortical actomyosin contractility during cytokinesis and other events. Here we report how two novel cytokinetic ring components, GCK-1 and CCM-3, participate in a negative feedback loop among RhoA and its cytoskeletal effectors to inhibit contractility. GCK-1 and CCM-3 are recruited by active RhoA and anillin to the cytokinetic ring, where they in turn limit RhoA activity and contractility. This is evidenced by increased RhoA activity, anillin and non-muscle myosin II in the cytokinetic ring, and faster cytokinetic furrowing, following depletion of GCK-1 or CCM-3. GCK-1 or CCM-3 depletion also reduced RGA-3 levels in pulses, and increased baseline RhoA activity and pulsed contractility during zygote polarization. Together, our findings suggest that GCK-1 and CCM-3 regulate cortical actomyosin contractility via negative feedback.Summary Novel cytokinetic ring proteins, the Ste20 family kinase GCK-1 and its heterodimeric cofactor 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 C. elegans zygote.Competing Interest StatementThe authors have declared no competing interest.