QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, March 14, 2007, 27(11):2938-2942; doi:10.1523/JNEUROSCI.4851-06.2007

This Article Full Text Full Text (PDF) Supplemental Data Submit an eLetter 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 Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (17) Citing Articles via Google Scholar Google Scholar Articles by Leary, G. P. Articles by Kavanaugh, M. P. Search for Related Content PubMed PubMed Citation Articles by Leary, G. P. Articles by Kavanaugh, M. P.

 Previous Article  |  Next Article 

Cellular/Molecular
The Glutamate and Chloride Permeation Pathways Are Colocalized in Individual Neuronal Glutamate Transporter Subunits

Gregory P. Leary,¹ Emily F. Stone,² David C. Holley,¹ and Michael P. Kavanaugh¹

Center for Structural and Functional Neuroscience, ¹Departments of Biomedical and Pharmaceutical Sciences and ²Mathematics, University of Montana, Missoula, Montana 59812

Correspondence should be addressed to Michael P. Kavanaugh, 301 Skaggs Building, University of Montana, Missoula, MT 59812. Email: michael.kavanaugh{at}umontana.edu

Glutamate transporters have a homotrimeric subunit structure with a large central water-filled cavity that extends partially into the plane of the lipid bilayer (Yernool et al., 2004). In addition to uptake of glutamate, the transporters also mediate a chloride conductance that is increased in the presence of substrate. Whether the chloride channel is located in the central pore of the trimer or within the individual subunits has been controversial. We find that coexpression of wild-type neuronal glutamate transporter EAAT3 subunits with subunits mutated at R447, a residue governing substrate selectivity (Bendahan et al., 2000), results in transport activity consistent with two distinct noninteracting populations of transporters, in agreement with previous work suggesting that each subunit operates independently to transport substrate (Awes et al., 2004; Grewer et al., 2005; Koch and Larsson, 2005). In wild-type homotrimeric transporters, the glutamate concentration dependence of the anion conductance and the kinetics of glutamate flux were isolated and measured, and the anion channel activation was fitted to analytical expressions corresponding to (1) a central pore gated by binding to one or more subunits and (2) a channel pore in each subunit. The data indicate that glutamate-binding sites, transport pathways, and chloride channels reside in individual subunits in a trimer and function independently.

Key words: glutamate receptor; glutamate transport; chloride channel; modeling; uptake; EAAT

---

Received Nov. 7, 2006; revised Feb. 7, 2007; accepted Feb. 8, 2007.

Correspondence should be addressed to Michael P. Kavanaugh, 301 Skaggs Building, University of Montana, Missoula, MT 59812. Email: michael.kavanaugh{at}umontana.edu

This article has been cited by other articles:

				S. Broer, H.-P. Schneider, A. Broer, and J. W. Deitmer Mutation of Asparagine 76 in the Center of Glutamine Transporter SNAT3 Modulates Substrate-induced Conductances and Na+ Binding J. Biol. Chem., September 18, 2009; 284(38): 25823 - 25831. [Abstract] [Full Text] [PDF]

				S. Teichman, S. Qu, and B. I. Kanner The equivalent of a thallium binding residue from an archeal homolog controls cation interactions in brain glutamate transporters PNAS, August 25, 2009; 106(34): 14297 - 14302. [Abstract] [Full Text] [PDF]

				Y. Gu, I. H. Shrivastava, S. G. Amara, and I. Bahar Molecular simulations elucidate the substrate translocation pathway in a glutamate transporter PNAS, February 24, 2009; 106(8): 2589 - 2594. [Abstract] [Full Text] [PDF]

				D. C Holley and M. P Kavanaugh Interactions of alkali cations with glutamate transporters Phil Trans R Soc B, January 27, 2009; 364(1514): 155 - 161. [Abstract] [Full Text] [PDF]

				I. H. Shrivastava, J. Jiang, S. G. Amara, and I. Bahar Time-resolved Mechanism of Extracellular Gate Opening and Substrate Binding in a Glutamate Transporter J. Biol. Chem., October 17, 2008; 283(42): 28680 - 28690. [Abstract] [Full Text] [PDF]

				S. Qu and B. I. Kanner Substrates and Non-transportable Analogues Induce Structural Rearrangements at the Extracellular Entrance of the Glial Glutamate Transporter GLT-1/EAAT2 J. Biol. Chem., September 26, 2008; 283(39): 26391 - 26400. [Abstract] [Full Text] [PDF]

				D. Torres-Salazar and C. Fahlke Neuronal Glutamate Transporters Vary in Substrate Transport Rate but Not in Unitary Anion Channel Conductance J. Biol. Chem., November 30, 2007; 282(48): 34719 - 34726. [Abstract] [Full Text] [PDF]

				A. Weise, H. M. Becker, and J. W. Deitmer Enzymatic Suppression of the Membrane Conductance Associated with the Glutamine Transporter SNAT3 Expressed in Xenopus Oocytes by Carbonic Anhydrase II J. Gen. Physiol., July 30, 2007; 130(2): 203 - 215. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help