RT Journal Article
SR Electronic
T1 Novel cytokinetic ring components drive negative feedback in cortical contractility
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 633743
DO 10.1101/633743
A1 Kathryn Rehain Bell
A1 Michael E. Werner
A1 Anusha Doshi
A1 Daniel B. Cortes
A1 Adam Sattler
A1 Thanh Vuong-Brender
A1 Michel Labouesse
A1 Amy Shaub Maddox
YR 2020
UL http://biorxiv.org/content/early/2020/05/03/633743.abstract
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.