ICAP-1 monoubiquitylation coordinates matrix density and rigidity sensing for cell migration through ROCK2–MRCKα balance - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Cell Science Année : 2017

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

Résumé

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.
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hal-02324086 , version 1 (21-10-2019)

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Anne-Pascale Bouin, Alexander Kyurmurkov, Myriam Régent-Kloeckner, Anne-Sophie Ribba, Eva Faurobert, et al.. ICAP-1 monoubiquitylation coordinates matrix density and rigidity sensing for cell migration through ROCK2–MRCKα balance. Journal of Cell Science, 2017, 130 (3), pp.626-636. ⟨10.1242/jcs.200139⟩. ⟨hal-02324086⟩
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