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J Cell Sci. 2017 Feb 1;130(3):626-636. doi: 10.1242/jcs.200139. Epub 2017 Jan 3.

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

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  • 1INSERM U1209, Grenoble F-38042, France.
  • 2Université Grenoble Alpes, Institute for Advanced Biosciences, Grenoble 38042, France.
  • 3CNRS UMR 5309, Grenoble F-38042, France.
  • 4Laboratoire Interdisciplinaire de Physique, UMR CNRS, Grenoble 5588, France.
  • 5INSERM U1209, Grenoble F-38042, France


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.


Cell contractility; Cell migration; ICAP-1; Integrin; Monoubiquitylation; Rigidity sensing

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