Identification of PA2.26 antigen as a novel cell-surface mucin-type glycoprotein that induces plasma membrane extensions and increased motility in keratinocytes

PA2.26 antigen was identified as a cell-surface protein induced in epiderma l carcinogenesis and skin remodeling processes. PA2,26 is expressed in carc inoma cell lines and cultured fibroblasts but absent in nontumorigenic kera tinocytes. In tissues, PA2,26 is present in epithelial cells of the choroid plexus, ependyma, glomerulus and alveolus, in mesothelial cells, and in en dothelia of lymphatic vessels. Biochemical characterization of PA2,26 prote in and sequence analysis of the isolated cDNA demonstrate that PA2,26 antig en is a mucin-like transmembrane glycoprotein. Confocal and immunoelectron microscopy analysis in cultured cells reveal that PA2,26 is concentrated in actin-rich microvilli and plasma membrane projections, such as filopodia, lamellipodia and ruffles, where it colocalizes with members of the ERM (ezr in, radixin, moesin) family protein. Ezrin and moesin, but not radixin, can be coimmunoprecipitated together with PA2,26 from cell lysates, Ectopic ex pression of PA2,26 in immortalized, nontumorigenic, keratinocytes induces a n epithelial-fibroblastoid morphological conversion with increased plasma m embrane extensions, concomitantly to a major reorganization of the actin cy toskeleton, redistribution of ezrin to cell-surface projections, and enhanc ed motility, These findings suggest an involvement of PA2,26 in cell migrat ion.