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First published online 19 February 2008
doi: 10.1242/jcs.017681

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Signal-dependent export of GABA transporter 1 from the ER-Golgi intermediate compartment is specified by a C-terminal motif

¹ Institute of Pharmacology, Center of Biomolecular Medicine and Pharmacology, Medical University of Vienna, Waehringer Str. 13a, 1090 Vienna, Austria
² Department of Pharmacology and Neurobiology, Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland
³ Department of Cell Biology and Ultrastructure Research, Center for Anatomy and Cell Biology, Medical University of Vienna, Schwarzspanierstr. 17, A-1090 Vienna, Austria

^* Author for correspondence (e-mail: michael.freissmuth{at}meduniwien.ac.at)

Accepted 4 December 2007

The C-terminus of GABA transporter 1 (GAT1, SLC6A1) is required for trafficking of the protein through the secretory pathway to reach its final destination, i.e. the rim of the synaptic specialization. We identified a motif of three hydrophobic residues (⁵⁶⁹VMI⁵⁷¹) that was required for export of GAT1 from the ER-Golgi intermediate compartment (ERGIC). This conclusion was based on the following observations: (i) GAT1-SSS, the mutant in which ⁵⁶⁹VMI⁵⁷¹ was replaced by serine residues, was exported from the ER in a COPII-dependent manner but accumulated in punctate structures and failed to reach the Golgi; (ii) under appropriate conditions (imposing a block at 15°C, disruption of COPI), these structures also contained ERGIC53; (iii) the punctae were part of a dynamic compartment, because it was accessible to a second anterograde cargo [the temperature-sensitive variant of vesicular stomatitis virus G protein (VSV-G)] and because GAT1-SSS could be retrieved from the punctate structures by addition of a KKxx-based retrieval motif, which supported retrograde transport to the ER. To the best of our knowledge, the VMI-motif of GAT1 provides the first example of a cargo-based motif that specifies export from the ERGIC.

Key words: GABA transporter-1, ER-to-Golgi trafficking, ERGIC