title: Protein kinase C δ regulates the release of collagen type I from vascular smooth muscle cells via regulation of Cdc42.
abstract: Collagen type I is the most abundant component of extracellular matrix in the arterial wall. Mice knocked out for the protein kinase C δ gene (PKCδ KO) show a marked reduction of collagen I in the arterial wall. The lack of PKCδ diminished the ability of arterial smooth muscle cells (SMCs) to secrete collagen I without significantly altering the intracellular collagen content. Moreover, the unsecreted collagen I molecules accumulate in large perinuclear puncta. These perinuclear structures colocalize with the trans-Golgi network (TGN) marker TGN38 and to a lesser degree with cis-Golgi marker (GM130) but not with early endosomal marker (EEA1). Associated with diminished collagen I secretion, PKCδ KO SMCs exhibit a significant reduction in levels of cell division cycle 42 (Cdc42) protein and mRNA. Restoring PKCδ expression partially rescues Cdc42 expression and collagen I secretion in PKCδ KO SMCs. Inhibition of Cdc42 expression or activity with small interfering RNA or secramine A in PKCδ WT SMCs eliminates collagen I secretion. Conversely, restoring Cdc42 expression in PKCδ KO SMCs enables collagen I secretion. Taken together, our data demonstrate that PKCδ mediates collagen I secretion from SMCs, likely through a Cdc42-dependent mechanism.
authors.affiliation: Division of Peripheral Vascular Surgery, Department of Surgery, University of Wisconsin-Madison, Madison, WI 53705, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Lengfeld
authors.forename: Qiwei
authors.initials: Q
authors.lastname: Wang
authors.forename: Andrew
authors.initials: A
authors.lastname: Zohlman
authors.forename: Susana
authors.initials: S
authors.lastname: Salvarezza
authors.forename: Stephanie
authors.initials: S
authors.lastname: Morgan
authors.forename: Jun
authors.initials: J
authors.lastname: Ren
authors.forename: Kaori
authors.initials: K
authors.lastname: Kato
authors.forename: Enrique
authors.initials: E
authors.lastname: Rodriguez-Boulan
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism*; D055786:Gene Knockout Techniques; D006056:Golgi Apparatus / Q000201:enzymology; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000201:enzymology* / Q000378:metabolism; D051745:Protein Kinase C-delta / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D014158:Transcription, Genetic; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D024042:Collagen Type I; D051745:Protein Kinase C-delta; D020764:cdc42 GTP-Binding Protein