title: The COOH-terminal tail of the GAT-2 GABA transporter contains a novel motif that plays a role in basolateral targeting.
abstract: The ability of polarized epithelia to perform vectorial transport depends on the asymmetrical distribution of transmembrane proteins among their plasma membrane domains. The establishment and maintenance of these polar distributions relies on molecular signals embedded in the proteins themselves and the interpretation of these signals by cellular sorting machinery. Using Madin-Darby canine kidney (MDCK) cells as an in vitro model of polarized epithelia, our laboratory has previously shown that the COOH-terminal cytoplasmic 22 amino acids of the GAT-2 isoform of the gamma-amino butyric acid (GABA) transporter are necessary for its basolateral distribution. We demonstrate that the COOH-terminal tail of the transporter can function as an autonomous basolateral distribution signal, independently of the rest of the transporter. We find that the three-amino acid PDZ domain-interacting motif at the COOH-terminus of GAT-2 is not necessary for its basolateral distribution. Instead, the more proximal seven amino acids are necessary both for targeting and for steady-state distribution. Because this sequence resembles no other known basolateral sorting information, we conclude that these seven amino acids contain a novel basolateral targeting and distribution motif.
authors.affiliation: Yale Univ. School of Medicine, 333 Cedar St., New Haven, CT 06511, USA. michael.caplan@yale.edu
authors.forename: Andrea
authors.initials: A
authors.lastname: Brown
authors.forename: Theodore
authors.initials: T
authors.lastname: Muth
authors.forename: Michael
authors.initials: M
authors.lastname: Caplan
mesh_terms: D020816:Amino Acid Motifs / Q000502:physiology; D000818:Animals; D002460:Cell Line; D004285:Dogs; D006706:Homeostasis; D007425:Intracellular Membranes / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D026901:Membrane Transport Proteins