title: Expression of Human MDGA1 Increases Cell Motility and Cell-Cell Adhesion and Reduces Adhesion to Extracellular Matrix Proteins in MDCK Cells.
abstract: Characterization of the novel human protein MDGA1 (MAM Domain containing Glycosylphosphatidylinositol Anchor-1) has been reported in our laboratory in the past few years. hMDGA1 is a glycoprotein containing 955 aminoacids (137 kDa) attached to the eukaryotic cell membrane by a GPI (Glycosylphosphatidylinositol) anchor and localized specifically into membrane microdomains known as lipid rafts. Moreover, MDGA1 protein contains structural features found in different types of cell adhesion molecules (CAMs) such as the presence of immunoglobulin domains and a MAM domain (Meprin, A5 protein, receptor protein-tyrosine phosphatase μ), suggesting a role of MDGA1 in cell migration and/or adhesion. In order to investigate this aim, stable MDCK cell lines expressing MDGA1 or the truncated proteins IgGPI (lacking the MAM domain) and MAMGPI (lacking Ig domains) were generated. Our results reveal that MDGA1 increases the ability of MDCK cells to migrate, as it contains both Ig and MAM domains which have been implicated in cell motility. In addition, cell adhesion to extracellular matrix proteins, mainly to collagen IV, is reduced by MDGA1 and the IgGPI and MAMGPI truncated proteins. Accordingly, silencing MDGA1 by siRNA revealed a significant increase in adhesion to collagen IV. Furthermore, MDGA1 expression, through the intrinsic properties of the MAM domain, increases cell-cell adhesion independently of the cell monolayer used, suggesting that MDGA1 mediates cell-cell adhesiveness in a heterophilic manner.
authors.forename: Antonio
authors.initials: A
authors.lastname: Díaz-López
authors.forename: Pilar
authors.initials: P
authors.lastname: Iniesta
authors.forename: Alberto
authors.initials: A
authors.lastname: Morán
authors.forename: Paloma
authors.initials: P
authors.lastname: Ortega
authors.forename: Tamara
authors.initials: T
authors.lastname: Fernández-Marcelo
authors.forename: Andrés
authors.initials: A
authors.lastname: Sánchez-Pernaute
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Torres
authors.forename: Manuel
authors.initials: M
authors.lastname: Benito
authors.forename: Carmen
authors.initials: C
authors.lastname: De Juan