TitleAnillin Promotes Cell Contractility by Cyclic Resetting of RhoA Residence Kinetics.
Publication TypeJournal Article
Year of Publication2019
AuthorsBudnar S, Husain KB, Gomez GA, Naghibosadat M, Varma A, Verma S, Hamilton NA, Morris RG, Yap AS
JournalDev Cell
Date Published2019 Jun 17

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-P (PIP) 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 PIP 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.

Alternate JournalDev. Cell
PubMed ID31105010