DIFFERENTIAL INTRACELLULAR SORTING OF THE MYELIN-ASSOCIATED GLYCOPROTEIN ISOFORMS

Myelin-associated glycoprotein (MAG), a myelin-specific protein, is ex pressed as two isoforms, designated as L-MAG and S-MAG. Both share ide ntical extracellular and transmembrane domains but differ in their cyt oplasmic domains. L-MAG is expressed earlier during myelination than S -MAG. These features, as well as others, suggest that the isoforms hav e different functions. To confirm this hypothesis, both isoforms were expressed transiently and stably in Madin-Darby canine kidney (MDCK) e pithelial cells, and the localization of the isoforms was studied. In both transiently and stably transfected cells, L-MAG sorted primarily to the basolateral membrane. In single transfected cells, S-MAG sorted primarily to the apical membrane. When groups of adjacent cells becam e transiently transfected, S-MAG accumulated at areas of cell-cell con tact within the basolateral membrane. In stably transfected cells S-MA G sorted to the basolateral membrane. The data suggest that L-MAG cont ains an invariable basolateral sorting signal, but that the sorting of S-MAG is dependent upon extrinsic factors, such as coexpression by ad jacent (contacting) cells. As MDCK cells sort the MAG isoforms differe ntly, these data support the hypothesis that the MAG isoforms do perfo rm different functions. (C) 1996 Wiley-Liss, Inc.