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

Anillin Promotes Cell Contractility by Cyclic Resetting of RhoA Residence Kinetics.

Author information

1
Division of Cell Biology and Molecular Medicine, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Brisbane, QLD 4072, Australia. Electronic address: s.budnar@imb.uq.edu.au.
2
Simons Centre for the Study of Living Machines, National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore 560065, India.
3
Division of Cell Biology and Molecular Medicine, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Brisbane, QLD 4072, Australia; Centre for Cancer Biology, SA, Pathology and University of South Australia, Adelaide, SA 5000, Australia.
4
Division of Cell Biology and Molecular Medicine, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Brisbane, QLD 4072, Australia.
5
Viravecs Laboratories CCAMP, GKVK Campus, Bellary Road, Bangalore, Karnataka 560065, India.
6
Simons Centre for the Study of Living Machines, National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore 560065, India; EMBL-Australia node in Single Molecule Science, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia. Electronic address: r.g.morris@unsw.edu.au.
7
Division of Cell Biology and Molecular Medicine, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, Brisbane, QLD 4072, Australia. Electronic address: a.yap@uq.edu.au.

Abstract

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

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