title: Role of coronin 1B in PDGF-induced migration of vascular smooth muscle cells.
abstract: BACKGROUND
  The type I subclass of coronins, a family of actin-binding proteins, regulates various actin-dependent cellular processes, including migration. However, the existence and role of coronins in vascular smooth muscle cell (VSMC) migration has yet to be determined.
  
  
  OBJECTIVE
  The goal of the present study was to define the mechanism by which coronins regulate platelet-derived growth factor (PDGF)-induced VSMC migration.
  
  
  RESULTS
  Coronin 1B (Coro1B) and 1C (Coro1C) were both found to be expressed in VSMCs at the mRNA and protein levels. Downregulation of Coro1B by siRNA increases PDGF-induced migration, while downregulation of Coro1C has no effect. We confirmed through kymograph analysis that the Coro1B-downregulation-mediated increase in migration is directly linked to increased lamellipodial protraction rate and protrusion distance in VSMC. In other cell types, coronins exert their effects on lamellipodia dynamics by an inhibitory interaction with the ARP2/3 complex, which is disrupted by the phosphorylation of Coro1B. We found that PDGF induces phosphorylation of Coro1B on serine-2 via PKCε, leading to a decrease in the interaction of Coro1B with the ARP2/3 complex. VSMCs transfected with a phosphodeficient S2A Coro1B mutant showed decreased migration in response to PDGF, suggesting that the phosphorylation of Coro1B is required for the promotion of migration by PDGF. In both the rat and mouse, Coro1B phosphorylation was increased in response to vessel injury in vivo.
  
  
  CONCLUSIONS
  Our data suggest that phosphorylation of Coro1B and the subsequent reduced interaction with ARP2/3 complex participate in PDGF-induced VSMC migration, an important step in vascular lesion formation.
authors.affiliation: Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Holly C
authors.initials: HC
authors.lastname: Williams
authors.forename: Alejandra
authors.initials: A
authors.lastname: San Martín
authors.forename: Candace M
authors.initials: CM
authors.lastname: Adamo
authors.forename: Bonnie
authors.initials: B
authors.lastname: Seidel-Rogol
authors.forename: Lily
authors.initials: L
authors.lastname: Pounkova
authors.forename: Srinivasan Raju
authors.initials: SR
authors.lastname: Datla
authors.forename: Bernard
authors.initials: B
authors.lastname: Lassègue
authors.forename: James E
authors.initials: JE
authors.lastname: Bear
authors.forename: Kathy
authors.initials: K
authors.lastname: Griendling
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism; D000818:Animals; D000077214:Becaplermin; D020212:Carotid Artery Injuries / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D007734:Kymography; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D009154:Mutation; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D058426:Neointima; D010766:Phosphorylation; D051744:Protein Kinase C-epsilon / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism*; D011554:Pseudopodia / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000378:metabolism; D012694:Serine; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D008840:Microfilament Proteins; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D011994:Recombinant Proteins; C072061:coronin proteins; D000077214:Becaplermin; D012694:Serine; C497257:Prkce protein, rat; D051744:Protein Kinase C-epsilon