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

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Bouin, Anne-Pascale | Kyurmurkov, Alexander | Régent-Kloeckner, Myriam | Ribba, Anne-Sophie | Faurobert, Eva | Fournier, Henri-Noël | Bourrin-Reynard, Ingrid | Manet-Dupé, Sandra | Oddou, Christiane | Balland, Martial | Planus, Emmanuelle | Albiges-Rizo, Corinne

Edité par CCSD ; Company of Biologists -

International audience. 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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