ICAP-1 monoubiquitylation coordinates matrix density and rigidity sensing for cell migration through ROCK2-MRCKα balance.

Abstract:

:Cell migration is a complex process requiring density and rigidity sensing of the microenvironment to adapt cell migratory speed through focal adhesion and actin cytoskeleton regulation. ICAP-1 (also known as ITGB1BP1), a β1 integrin partner, is essential for ensuring integrin activation cycle and focal adhesion formation. We show that ICAP-1 is monoubiquitylated by Smurf1, preventing ICAP-1 binding to β1 integrin. The non-ubiquitylatable form of ICAP-1 modifies β1 integrin focal adhesion organization and interferes with fibronectin density sensing. ICAP-1 is also required for adapting cell migration in response to substrate stiffness in a β1-integrin-independent manner. ICAP-1 monoubiquitylation regulates rigidity sensing by increasing MRCKα (also known as CDC42BPA)-dependent cell contractility through myosin phosphorylation independently of substrate rigidity. We provide evidence that ICAP-1 monoubiquitylation helps in switching from ROCK2-mediated to MRCKα-mediated cell contractility. ICAP-1 monoubiquitylation serves as a molecular switch to coordinate extracellular matrix density and rigidity sensing thus acting as a crucial modulator of cell migration and mechanosensing.

journal_name

J Cell Sci

journal_title

Journal of cell science

authors

Bouin AP,Kyumurkov A,Régent-Kloeckner M,Ribba AS,Faurobert E,Fournier HN,Bourrin-Reynard I,Manet-Dupé S,Oddou C,Balland M,Planus E,Albiges-Rizo C

doi

10.1242/jcs.200139

subject

Has Abstract

pub_date

2017-02-01 00:00:00

pages

626-636

issue

3

eissn

0021-9533

issn

1477-9137

pii

jcs.200139

journal_volume

130

pub_type

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