Tetraspanin CD9 regulates cell contraction and actin arrangement via RhoA in human vascular smooth muscle cells

• Published in: PloS one 2014-09, Vol.9 (9), p.e106999-e106999
• Main Authors: Herr, Michael J, Mabry, Scott E, Jennings, Lisa K
• Format: Article
• Language: English
• Subjects: Actin; Actins - genetics; Actins - metabolism; Aorta; Biochemistry; Biology; Biology and life sciences; Cardiovascular diseases; CD9 antigen; Cell adhesion & migration; Cell culture; Cells, Cultured; Contraction; Cytology; Genotype & phenotype; Growth factors; GTP; Guanosine triphosphate; Heart diseases; Humans; Hypertension; Immunoglobulins; Immunology; Internal medicine; Kinases; Laboratories; Motility; Muscle Contraction; Muscle proteins; Muscles; Myocytes, Smooth Muscle - metabolism; Myocytes, Smooth Muscle - pathology; Plasmids; Proteins; Restoration; rhoA GTP-Binding Protein - genetics; rhoA GTP-Binding Protein - metabolism; RhoA protein; Rodents; Science; Signal Transduction; Signaling; Smooth muscle; Tetraspanin-29 - genetics; Tetraspanin-29 - metabolism; Vascular Diseases - genetics; Vascular Diseases - metabolism; Vascular Diseases - pathology; Vascular Diseases - physiopathology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0106999

The most prevalent cardiovascular diseases arise from alterations in vascular smooth muscle cell (VSMC) morphology and function. Tetraspanin CD9 has been previously implicated in regulating vascular pathologies; however, insight into how CD9 may regulate adverse VSMC phenotypes has not been provided. We utilized a human model of aortic smooth muscle cells to understand the consequences of CD9 deficiency on VSMC phenotypes. Upon knocking down CD9, the cells developed an abnormally small and rounded morphology. We determined that this morphological change was due to a lack of typical parallel actin arrangement. We also found similar total RhoA but decreased GTP-bound (active) RhoA levels in CD9 deficient cells. As a result, cells lacking a full complement of CD9 were less contractile than their control treated counterparts. Upon restoration of RhoA activity in the CD9 deficient cells, the phenotype was reversed and cell contraction was restored. Conversely, inhibition of RhoA activity in the control cells mimicked the CD9-deficient cell phenotype. Thus, alteration in CD9 expression was sufficient to profoundly disrupt cellular actin arrangement and endogenous cell contraction by interfering with RhoA signaling. This study provides insight into how CD9 may regulate previously described vascular smooth muscle cell pathophysiology.