title: The tetraspanin CD151 regulates cell morphology and intracellular signaling on laminin-511.
abstract: The tetraspanin CD151 forms a stable complex with integrin alpha3beta1, a widely expressed laminin receptor, and is implicated in the regulation of integrin alpha3beta1-mediated cellular responses, including cell attachment, spreading and migration. However, the molecular mechanism by which CD151 regulates integrin alpha3beta1 functions remains unclear. To address this issue, we knocked down CD151 expression in A549 human lung adenocarcinoma cells by RNA interference. When plated on laminin-511 (laminin-10), the CD151-knocked-down cells showed aberrant membrane protrusions and exhibited reductions in the tyrosine phosphorylation of focal adhesion kinase, Src, p130Cas and paxillin. The formation of membrane protrusions was attenuated when the cells were either plated on surfaces coated with higher concentrations of laminin-511 or treated with the integrin beta1-activating mAb TS2/16; however, neither treatment could rescue the reduced tyrosine phosphorylation. These results indicate that CD151 knockdown weakens the integrin alpha3beta1-mediated adhesion to laminin-511 and thereby provokes an aberrant morphology, but this reduced adhesive activity is not involved in the decline of signaling events in CD151-knocked-down cells. Thus, our results suggest that CD151 regulates integrin alpha3beta1 functions in two independent aspects: potentiation of integrin alpha3beta1-mediated cell adhesion and promotion of integrin alpha3beta1-stimulated signaling events involving tyrosine phosphorylation.
authors.affiliation: Laboratory of Extracellular Matrix Biochemistry, Institute for Protein Research, Osaka University, Suita, Osaka, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Yamada
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Sumida
authors.forename: Akemi
authors.initials: A
authors.lastname: Fujibayashi
authors.forename: Kiyomitsu
authors.initials: K
authors.lastname: Fukaguchi
authors.forename: Noriko
authors.initials: N
authors.lastname: Sanzen
authors.forename: Ryoko
authors.initials: R
authors.lastname: Nishiuchi
authors.forename: Kiyotoshi
authors.initials: K
authors.lastname: Sekiguchi
mesh_terms: D015703:Antigens, CD / Q000502:physiology*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D039201:Integrin alpha3beta1 / Q000737:chemistry*; D007797:Laminin / Q000737:chemistry*; D008024:Ligands; D010766:Phosphorylation; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D060185:Tetraspanin 24; D014162:Transfection; D014443:Tyrosine / Q000737:chemistry
chemical_list: D015703:Antigens, CD; C554715:CD151 protein, human; D039201:Integrin alpha3beta1; D007797:Laminin; D008024:Ligands; D034741:RNA, Small Interfering; D060185:Tetraspanin 24; D014443:Tyrosine