title: The Caenorhabditis elegans snf-11 gene encodes a sodium-dependent GABA transporter required for clearance of synaptic GABA.
abstract: Sodium-dependent neurotransmitter transporters participate in the clearance and/or recycling of neurotransmitters from synaptic clefts. The snf-11 gene in Caenorhabditis 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 value of 168 microM, 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 postsynaptic (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 that the localization of SNF-11 is consistent with a GABA clearance function rather than recycling.
authors.affiliation: Program in Molecular, Cell, and Developmental Biology, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Mullen
authors.forename: Eleanor A
authors.initials: EA
authors.lastname: Mathews
authors.forename: Paurush
authors.initials: P
authors.lastname: Saxena
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Fields
authors.forename: John R
authors.initials: JR
authors.lastname: McManus
authors.forename: Gary
authors.initials: G
authors.lastname: Moulder
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Barstead
authors.forename: Michael W
authors.initials: MW
authors.lastname: Quick
authors.forename: James B
authors.initials: JB
authors.lastname: Rand
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000737:chemistry / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D018682:GABA Agents / Q000494:pharmacology; D050485:GABA Plasma Membrane Transport Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D017238:Genes, Helminth / Q000502:physiology*; D009154:Mutation; D009557:Nipecotic Acids / Q000494:pharmacology; D010641:Phenotype; D010802:Phylogeny; D012964:Sodium / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D018682:GABA Agents; D050485:GABA Plasma Membrane Transport Proteins; D009557:Nipecotic Acids; C513354:Snf-11 protein, C elegans; D005680:gamma-Aminobutyric Acid; C045598:N-(4,4-diphenyl-3-butenyl)nipecotic acid; D012964:Sodium