Anillin Promotes Cell Contractility by Cyclic Resetting of RhoA Residence Kinetics

Dev Cell. 2019 Jun 17;49(6):894-906.e12. doi: 10.1016/j.devcel.2019.04.031. Epub 2019 May 16.


RhoA stimulates cell contractility by recruiting downstream effectors to the cortical plasma membrane. We now show that direct binding by anillin is required for effective signaling: this antagonizes the otherwise labile membrane association of GTP-RhoA to promote effector recruitment. However, since its binding to RhoA blocks access by other effectors, we demonstrate that anillin must also concentrate membrane phosphoinositide-4,5-P2 (PIP2) to promote signaling. We propose and test a sequential pathway where GTP-RhoA first binds to anillin and then is retained at the membrane by PIP2 after it disengages from anillin. Importantly, re-binding of membrane GTP-RhoA to anillin, regulated by the cortical density of anillin, creates cycles through this pathway. These cycles repeatedly reset the dissociation kinetics of GTP-RhoA, substantially increasing its dwell time to recruit effectors. Thus, anillin regulates RhoA signaling by a paradigm of kinetic scaffolding that may apply to other signals whose efficacy depends on their cortical dwell times.

Keywords: GTPases and junctional tension; PI(4,5)P(2); ROCK1; RhoA; Scaffold; anillin; contractility; mDia1; resetting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Cell Movement / drug effects*
  • Contractile Proteins / pharmacology*
  • Cytokinesis / drug effects
  • Cytokinesis / physiology*
  • Female
  • Guanosine Triphosphate / metabolism*
  • Humans
  • Kinetics
  • MCF-7 Cells
  • Phosphatidylinositol 4,5-Diphosphate / metabolism*
  • Signal Transduction
  • rhoA GTP-Binding Protein / genetics
  • rhoA GTP-Binding Protein / metabolism*


  • Contractile Proteins
  • Phosphatidylinositol 4,5-Diphosphate
  • anillin
  • RHOA protein, human
  • Guanosine Triphosphate
  • rhoA GTP-Binding Protein