PDGF‐induced Vascular Smooth Muscle Cell Migration is Regulated by Coronin 1b

Abstract

Platelet derived growth factor (PDGF) plays a pivotal role in cardiovascular disease progression, partially by initiating vascular smooth muscle cell (VSMC) migration. Recent studies show that the actin binding protein coronin 1b can regulate actin polymerization and depolymerization via phosphorylation‐regulated binding to Arp2/3 and Slingshot phosphatase (SSH1L). In this study a possible role for coronin 1b in PDGF‐induced VSMC migration was examined. PDGF (10 ng/ml)‐stimulated coronin 1b phosphorylation peaked at 5 minutes (11.8±1.3‐fold above basal) and was maintained for up to 60 minutes. The PKC inhibitors Ro‐32‐0432 (0.5 μM) and GÖ 6976 (0.5 μM) attenuated PDGF‐ induced coronin 1b phosphorylation (88±10% and 72±2%, respectively), implicating PKC‐α or PKC‐β in the phosphorylation response. PDGF stimulation of VSMCs decreased coronin 1b and ArpC2 (a subunit of Arp2/3) interactions at 5–10 min, as determined by co‐immunoprecipitation, but no effect of PDGF on coronin 1b‐SSH1L interaction was observed. Functionally, transfection with siRNA against coronin 1b completely inhibited PDGF‐induced VSMC migration, as measured by modified Boyden chamber assay. These data suggest that PDGF may signal to coronin to coordinate lamellipodia formation and thus migration in VSMCs, and suggest a new therapeutic target for vasculopathies with a significant migratory component.