부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.yexcr.2009.09.022 Byline: Magnus C. Lydolph, Marie Morgan-Fisher, Anette M. HA[cedilla]ye, John R. Couchman, Ulla M. Wewer, Atsuko Yoneda Keywords: [alpha]9[beta]1 integrin; Cell migration; Focal adhesion; Cytoskeleton; Small GTPase; ADAM12 Abstract: Cell surface integrins are the primary receptors for cell migration on extracellular matrix, and exist in several activation states regulated in part by ectodomain conformation. The [alpha]9 integrin subunit, which pairs only with [beta]1, has specific roles in the immune system and may regulate cell migration. Melanoma cells express abundant [alpha]9[beta]1 integrin, and its role in cell migration was assessed. Ligands derived from Tenascin-C and ADAM12 supported [alpha]9[beta]1 integrin-mediated cell attachment and GTP-Rac dependent migration, but not focal adhesion formation. Manganese ions induced [alpha]9[beta]1 integrin- and Rho kinase-dependent focal adhesion and stress fibre formation, suggesting that the activation status of [alpha]9[beta]1 integrin was altered. The effect of manganese ions in promoting focal adhesion formation was reproduced by [beta]1 integrin activating antibody. The [alpha]9[beta]1 integrin translocated to focal adhesions, where active [beta]1 integrin was also detected by conformation-specific antibodies. Focal adhesion assembly was commensurate with reduced cell migration. Endogenous [alpha]9[beta]1 integrin-mediated adhesion was sensitive to the PP1 chemical inhibitor and an inhibitor of endosomal vesicle recycling, but not inhibitors of protein kinase C or the small GTPase Rho. Our results demonstrated that although [alpha]9[beta]1 integrin can induce and localise to focal adhesions in a high activation state, its intermediate activity state normally supports cell adhesion consistent with migration. Author Affiliation: Department of Biomedical Sciences, The Faculty of Health Sciences, and Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen Biocenter, Ole MaalA[cedilla]es Vej 5, 2200 Copenhagen N, Denmark Article History: Received 16 April 2009; Revised 17 August 2009; Accepted 23 September 2009