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Fonction et régulation de la protéine ICAP-1alpha dans la dynamique de l'adhérence cellulaire dépendante des intégrines à chaîne beta1

Abstract : Cell adhesion to extracellular matrix mediated by integrins is a highly regulated dynamics process which allows cell motility. Among integrins regulators, ICAP-1alpha interacts with beta1 integrin cytoplasmic tail and disrupts adhesion sites. Since ICAP-1alpha is not localized into adhesions, it could reflects a transitory and finely regulated action onto beta1 integrin. In the first part of my work, I shown that ICAP-1alpha specifically slow-downs adhesion assembly by maintaining the low affinity state of beta1 integrin. Surprisingly, I found an unexpected function of ICAP-1alpha in the sensing of low extracellular matrix densities and in the adaptation of cell adhesive response to this environment. ICAP-1alpha acts as a mechanosensor which limits adhesion sites assembly and slow-downs cell adhesion and migration on low matrix densities. In a second part, I characterized the signaling pathway controlling ICAP-1 activity on beta1 integrin function. ICAP-1alpha is a phosphoprotein which displays different putative phosphorylation sites and one is potentially recognized by the calcium/calmodulin dependant protein kinase II, CaMKII. Many evidences reveal CaMKII implication in the regulation of ICAP-1alpha function. ICAP-1alpha phosphorylation on the CaMKII site induces its interaction onto beta1 integrin. CaMKII activity reduces the formation of adhesion complexes by promoting ICAP-1alpha binding onto beta1 integrin and by maintaining its low affinity state.
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https://tel.archives-ouvertes.fr/tel-00435843
Contributor : Angélique Millon Fremillon <>
Submitted on : Tuesday, November 24, 2009 - 10:31:53 PM
Last modification on : Friday, November 6, 2020 - 4:12:59 AM
Long-term archiving on: : Thursday, June 17, 2010 - 7:24:05 PM

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  • HAL Id : tel-00435843, version 1

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Angélique Millon-Fremillon. Fonction et régulation de la protéine ICAP-1alpha dans la dynamique de l'adhérence cellulaire dépendante des intégrines à chaîne beta1. Biologie cellulaire. Université Joseph-Fourier - Grenoble I, 2009. Français. ⟨tel-00435843⟩

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