FAK-mediated inhibition of vascular smooth muscle cell migration by the tetraspanin CD9.
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 in hibits SMC migration by a stimulation of both stress fiber formation and integrin clustering, leading to a stimulation of FAK phosphorylation.
Scherberich
Arnaud
A
Pharmacologie et Physico-Chime des Interactions Cellulaires et Moléculaires, UMR CNRS 7034, Faculté de Pharmacie, Université Louis Pasteur de Strasbourg, Illkirch, France.
Giannone
Grégory
G
Perennou
Elisabeth
E
Takeda
Kenneth
K
Boucheix
Claude
C
Rubinstein
Eric
E
Lanza
François
F
Beretz
Alain
A
D000199:Actins / Q000648:ultrastructure; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism / Q000502:physiology*; D020013:Calcium Signaling; D002465:Cell Movement; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D022001:Focal Adhesions; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism / Q000502:physiology*; D060245:Tetraspanin 29
D000199:Actins; D015703:Antigens, CD; C554869:CD9 protein, human; C554870:Cd9 protein, mouse; D008562:Membrane Glycoproteins; D060245:Tetraspanin 29; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496051:Ptk2 protein, mouse