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MBC in Press, published online ahead of print April 26, 2006
Mol. Biol. Cell 10.1091/mbc.E06-02-0155

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Submitted on February 24, 2006
Revised on April 10, 2006
Accepted on April 14, 2006

The Caenorhabditis elegans snf-11 Gene Encodes a Sodium-dependent GABA Transporter Required for Clearance of Synaptic GABA

Gregory P. Mullen,* Eleanor A. Mathews,* Paurush Saxena,{dagger} Stephen D. Fields,* John R. McManus,* Gary Moulder,* Robert J. Barstead,* Michael W. Quick,{dagger} and James B. Rand*

*Program in Molecular, Cell, and Developmental Biology, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104; {dagger}Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089-2520

Monitoring Editor: Sandra Schmid

Sodium-dependent neurotransmitter transporters participate in the clearance and/or recycling of neurotransmitters from synaptic clefts. The snf-11 gene in C. elegans encodes a protein of high similarity to mammalian GABA transporters (GATs). We show here that snf-11 encodes a functional GABA transporter; SNF-11-mediated GABA transport is Na+- and Cl--dependent, has an EC50 of 168 µM, and is blocked by the GAT1 inhibitor SKF89976A. The SNF-11 protein is expressed in seven GABAergic neurons, several additional neurons in the head and retrovesicular ganglion, and three groups of muscle cells. Therefore, all GABAergic synapses are associated with either presynaptic or post-synaptic (or both) expression of SNF-11. Although a snf-11 null mutation has no obvious effects on GABAergic behaviors, it leads to resistance to inhibitors of acetylcholinesterase. In vivo, a snf-11 null mutation blocks GABA uptake in at least a subset of GABAergic cells; in a cell culture system, all GABA uptake is abolished by the snf-11 mutation. We conclude that GABA transport activity is not essential for normal GABAergic function in C. elegans; and the localization of SNF-11 is consistent with a GABA clearance function rather than recycling.


Address correspondence to: James B. Rand (James-Rand{at}omrf.ouhsc.edu)




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