title: Transmembrane Protein 184A Is a Receptor Required for Vascular Smooth Muscle Cell Responses to Heparin.
abstract: Vascular cell responses to exogenous heparin have been documented to include decreased vascular smooth muscle cell proliferation following decreased ERK pathway signaling. However, the molecular mechanism(s) by which heparin interacts with cells to induce those responses has remained unclear. Previously characterized monoclonal antibodies that block heparin binding to vascular cells have been found to mimic heparin effects. In this study, those antibodies were employed to isolate a heparin binding protein. MALDI mass spectrometry data provide evidence that the protein isolated is transmembrane protein 184A (TMEM184A). Commercial antibodies against three separate regions of the TMEM184A human protein were used to identify the TMEM184A protein in vascular smooth muscle cells and endothelial cells. A GFP-TMEM184A construct was employed to determine colocalization with heparin after endocytosis. Knockdown of TMEM184A eliminated the physiological responses to heparin, including effects on ERK pathway activity and BrdU incorporation. Isolated GFP-TMEM184A binds heparin, and overexpression results in additional heparin uptake. Together, these data support the identification of TMEM184A as a heparin receptor in vascular cells.
authors.affiliation: Chemistry, Lehigh University, Bethlehem, Pennsylvania 18015.
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Pugh
authors.affiliation: From the Departments of Biological Sciences and the Department of Natural Sciences, DeSales University, Center Valley, Pennsylvania 18034.
authors.forename: Joshua B
authors.initials: JB
authors.lastname: Slee
authors.affiliation: From the Departments of Biological Sciences and.
authors.forename: Sara Lynn N
authors.initials: SL
authors.lastname: Farwell
authors.affiliation: From the Departments of Biological Sciences and.
authors.forename: Yaqiu
authors.initials: Y
authors.lastname: Li
authors.affiliation: From the Departments of Biological Sciences and.
authors.forename: Trista
authors.initials: T
authors.lastname: Barthol
authors.affiliation: the Department of Chemistry, Lebanon Valley College, Annville, Pennsylvania 17003, and.
authors.forename: Walter A
authors.initials: WA
authors.lastname: Patton
authors.affiliation: From the Departments of Biological Sciences and ljl0@lehigh.edu.
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Lowe-Krentz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D051381:Rats; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D011956:Receptors, Cell Surface; C000609638:Tmem184a protein, rat; D006493:Heparin
keywords: ERK; heparin-binding protein; receptor; signal transduction; vascular smooth muscle cells