SORTING OF 2 POLYTOPIC PROTEINS, THE GAMMA-AMINOBUTYRIC-ACID AND BETAINE TRANSPORTERS, IN POLARIZED EPITHELIAL-CELLS

The gamma-aminobutyric acid transporter (GAT-1) isoform of the gamma-a minobutyric acid and the betaine (BGT) transporters exhibit distinct a pical and basolateral distributions when introduced into Madin-Darby c anine kidney cells (Pietrini, G., Suh, Y. J., Edelman, L., Rudnick, G. , and Caplan, M. J. (1994) J. Biol. Chem. 269, 4668-4674), We have inv estigated the presence of sorting signals in their COOH-terminal cytos olic domains by expression in Madin-Darby canine kidney cells of mutat ed and chimeric transporters, Whereas truncated GAT-1 (Delta C-GAT) ma intained the original functional activity and apical localization, eit her the removal (Delta C-myc BGT) or the substitution (BGS chimera) of the cytosolic tail of BGT generated proteins that accumulated in the endoplasmic reticulum, Moreover, we have found that the cytosolic tail of BGT redirected apical proteins, the polytopic GAT-1 (GBS chimera) and the monotopic human nerve growth factor receptor, to the basolater al surface, These results suggest the presence of basolateral sorting information in the cytosolic tail of BGT. We have further shown that i nformation necessary for the exit of BGT from the endoplasmic reticulu m and for the basolateral localization of the GBS chimera is contained in a short segment, rich in basic residues, within the cytosolic tail of BGT.