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Am J Physiol Cell Physiol 286: C1071-C1077, 2004. First published December 18, 2003; doi:10.1152/ajpcell.00291.2003
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PROTEIN AND VESICLE TRAFFICKING, CYTOSKELETON

The COOH-terminal tail of the GAT-2 GABA transporter contains a novel motif that plays a role in basolateral targeting

Andrea Brown,1 Theodore Muth,2 and Michael Caplan1

1Yale University School of Medicine, New Haven, Connecticut 06511; and 2Brooklyn College, Brooklyn, New York 11210

Submitted 9 July 2003 ; accepted in final form 10 December 2003

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.

GABA transporter; traffic; sorting signal; targeting signal



Address for reprint requests and other correspondence: M. Caplan, Yale Univ. School of Medicine, 333 Cedar St., New Haven, CT 06511 (E-mail: michael.caplan{at}yale.edu).




This article has been cited by other articles:


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Mol. Biol. CellHome page
M. Carmosino, I. Gimenez, M. Caplan, and B. Forbush
Exon Loss Accounts for Differential Sorting of Na-K-Cl Cotransporters in Polarized Epithelial Cells
Mol. Biol. Cell, October 1, 2008; 19(10): 4341 - 4351.
[Abstract] [Full Text] [PDF]




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