Identification of MAGI-3 as a transforming growth factor-[alpha] tail binding protein

• Published in: Experimental cell research Vol. 303; no. 2; p. 457
• Main Authors: Franklin, Jeffrey L, Yoshiura, Kenta, Dempsey, Peter J, Bogatcheval, Galina, Jeyakumar, Loice, Meise, Katherine S, Pearsall, R Scott, Threadgill, David, Coffey, Robert J
• Format: Journal Article
• Language: English
• Published: New York Elsevier BV 15.02.2005
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2004.10.007

The cytoplasmic domain of the transforming growth factor-[alpha] precursor (proTGF[alpha]) contains a C-terminal PSD-95/SAP90, Discs Large, and Zona Occludens-1 (PDZ) recognition motif (TVV). By yeast two-hybrid screening of a mouse embryo library, we have found that a third member of a family of PDZ-containing proteins, membrane associated guanylate kinase inverted-3 (MAGI-3), binds to TGF[alpha]'s TVV. MAGI-3 is widely expressed in multiple mouse tissues, including brain. Immunolocalization showed that MAGI-3 and TGF[alpha] were colocalized in neurons in the cortex and dentate gyrus, as well as in ependymal cells and some astrocytes. In vitro, proTGF[alpha] bound the PDZ-1 domain of MAGI-3 and MAGI-2, but not MAGI-1. MAGI-3 and the 17-kDa cell surface form of proTGF[alpha] interact transiently in MDCK cells stably transfected with both MAGI-3 and human proTGF[alpha] cDNAs. MAGI-3 and wild-type proTGF[alpha] colocalize at the cell surface. In contrast, MAGI-3 forms a stable complex with membrane-fixed TGF[alpha] early in the secretory pathway and interacts with immature and cell surface forms of membrane-fixed TGF[alpha]. Overexpression of MAGI-3 resulted in increased levels of TGF[alpha] in the basolateral medium of polarized MDCK cells, suggesting that MAGI-3 has a role in efficient trafficking of TGF[alpha] to the cell surface in polarized epithelial cells. [PUBLICATION ABSTRACT]