Polarized distribution of glycine transporter isoforms in epithelial and neuronal cells

Asymmetrical distribution of Na+- and Cl--dependent neurotransmitter transp orters on the cell surface of polarized cells seems to be a generalized fea ture in this gene family. In the present study we analyzed the subcellular distribution of the various isoforms of the glycine transporters GLYT1 and GLYT2 after heterologous expression in polarized MDCK cells and in hippocam pal neurons. Our results indicate that glycine transporters are asymmetrica lly distributed in an isoform- and cell-type-specific manner. GLYT1b is loc alized in the basolateral and somatodendritic domains of MDCK cells and neu rons, respectively. However, GLYT1a is somatodendritic in neurons but is pr edominantly expressed in the apical surface of MDCK cells. The two isoforms of GLYT2 (GLYT2a and GLYT2b) are found at the apical surface in epithelial cells but are uniformly distributed in neurons. By using site-directed mut agenesis we have been able to identify signals for basolateral/somatodendri tic localization in the aminoterminal region of GLYT1 and in two dileucine motifs located in the carboxyl tail of this protein. These results contribu te to defining the mechanisms of asymmetrical distribution of transporters on the cell surface of polarized cells.