FAK-mediated Inhibition of Vascular Smooth Muscle Cell Migration by the Tetraspanin CD9

Summary

Migration of vascular smooth muscle cells (SMC) towards the intima is a key event in vascular proliferative diseases. We investigated a potential role for the tetraspanin CD9 in this process in a wound migration assay. Aortic SMC from CD9 knock-out mice had higher migration rates and the presumably stimulatory anti-CD9 antibody ALMA-1 inhibited migration of human SMC. The signaling pathways responsible for this inhibitory effect were investigated. In migrating CD9−/− SMC, stress fiber formation was decreased and focal adhesions were smaller and more diffusely distributed, consistent with an inhibition of integrin clustering. In migrating mouse SMC expressing CD9, focal adhesion kinase (FAK) tyrosine phosphorylation was doubled. No differences in intracellular calcium signaling were observed between CD9+/+ and CD9−/− SMC during migration. We suggest that CD9 inhibits SMC migration by a stimulation of both stress fiber formation and integrin clustering, leading to a stimulation of FAK phosphorylation.

Keywords

CD9 - tetraspanin - cell migration - smooth muscle - integrin - FAK - collagen

^* Present address: Friedrich Miescher Institute for Biomedical Research, Maulbeerstraße 66, CH-4058 Basel, Switzerland

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