HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 3, 2065-2077, January 21, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/3/2065    most recent M408470200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jiang, G. Articles by Ganapathy, V. Search for Related Content PubMed PubMed Citation Articles by Jiang, G. Articles by Ganapathy, V. Social Bookmarking                      What's this?

A Na⁺/Cl^–-coupled GABA Transporter, GAT-1, from Caenorhabditis elegans

STRUCTURAL AND FUNCTIONAL FEATURES, SPECIFIC EXPRESSION IN GABA-ERGIC NEURONS, AND INVOLVEMENT IN MUSCLE FUNCTION^*

Guoliang Jiang, Lina Zhuang, Seiji Miyauchi, Katsuya Miyake, You-Jun Fei, and Vadivel Ganapathy¶

From the Department of Biochemistry and Molecular Biology and Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia 30912

GABA functions as an inhibitory neurotransmitter in body muscles and as an excitatory neurotransmitter in enteric muscles in Caenorhabditis elegans. Whereas many of the components of the GABA-ergic neurotransmission in this organism have been identified at the molecular and functional levels, no transporter specific for this neurotransmitter has been identified to date. Here we report on the cloning and functional characterization of a GABA transporter from C. elegans (ceGAT-1) and on the functional relevance of the transporter to the biology of body muscles and enteric muscles. ceGAT-1 is coded by snf-11 gene, a member of the sodium-dependent neurotransmitter symporter gene family in C. elegans. The cloned ceGAT-1 functions as a Na⁺/Cl^–-coupled high-affinity transporter selective for GABA with a K_t of 15 µM. The Na⁺:Cl^–:GABA stoichiometry for ceGAT-1-mediated transport process is 2:1:1. The transport process is electrogenic as evidenced from GABA-induced inward currents in Xenopus laevis oocytes that express ceGAT-1 heterologously. The transporter is expressed exclusively in GABA-ergic neurons and in two other additional neurons. We also investigated the functional relevance of ceGAT-1 to the biology of body muscles and enteric muscles by ceGAT-1-specific RNA interference (RNAi) in rrf-3 mutant, a strain of C. elegans in which neurons are not refractory to RNAi as in the wild type strain. The down-regulation of ceGAT-1 by RNAi leads to an interesting phenotype associated with altered function of body muscles (as evident from changes in thrashing frequency) and enteric muscles (as evident from the rates of defecation failure) and also with altered sensitivity to aldicarb-induced paralysis. These findings provide unequivocal evidence for a modulatory role of GABA and ceGAT-1 in the biology of cholinergic neurons and in the function of body muscles and enteric muscles in this organism.

Received for publication, July 26, 2004 , and in revised form, November 8, 2004.

^* This work was supported in part by the National Institutes of Health Grants HD44404, HL64196, AI49849 (to V. G.), and AG22468 (to Y.-J. F.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) AY529124.

^¶ To whom correspondence should be addressed. E-mail: vganapat{at}mail.mcg.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. J. Kimber, S. McKinney, S. McMaster, T. A. Day, C. C. Fleming, and A. G. Maule flp gene disruption in a parasitic nematode reveals motor dysfunction and unusual neuronal sensitivity to RNA interference FASEB J, April 1, 2007; 21(4): 1233 - 1243. [Abstract] [Full Text] [PDF]

				G. P. Mullen, E. A. Mathews, P. Saxena, S. D. Fields, J. R. McManus, G. Moulder, R. J. Barstead, M. W. Quick, and J. B. Rand The Caenorhabditis elegans snf-11 Gene Encodes a Sodium-dependent GABA Transporter Required for Clearance of Synaptic GABA Mol. Biol. Cell, July 1, 2006; 17(7): 3021 - 3030. [Abstract] [Full Text] [PDF]