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Originally published In Press as doi:10.1074/jbc.M303258200 on May 22, 2003

J. Biol. Chem., Vol. 278, Issue 32, 30294-30301, August 8, 2003
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Membrane Topology of a Metabotropic Glutamate Receptor*

Gautam Bhave {ddagger} § §§, Brian M. Nadin {ddagger} §, D. J. Brasier {ddagger}, Kathi S. Glauner {ddagger} ¶, Ruchir D. Shah {ddagger} ||, Stephen F. Heinemann **, Farzana Karim {ddagger} and Robert W. Gereau , IV {ddagger} {ddagger}{ddagger}

From the {ddagger}Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030 and the **Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037

The metabotropic glutamate receptors (mGluRs) have been predicted to have a classical seven transmembrane domain structure similar to that seen for members of the G-protein-coupled receptor (GPCR) superfamily. However, the mGluRs (and other members of the family C GPCRs) show no sequence homology to the rhodopsin-like GPCRs, for which this seven transmembrane domain structure has been experimentally confirmed. Furthermore, several transmembrane domain prediction algorithms suggest that the mGluRs have a topology that is distinct from these receptors. In the present study, we set out to test whether mGluR5 has seven true transmembrane domains. Using a variety of approaches in both prokaryotic and eukaryotic systems, our data provide stong support for the proposed seven transmembrane domain model of mGluR5. We propose that this membrane topology can be extended to all members of the family C GPCRs.


Received for publication, March 28, 2003 , and in revised form, May 14, 2003.

* This work was supported by Grant MH60230 from the National Institutes of Health and the Gillson-Longenbaugh Foundation (to R. W. G.). 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.

§ These authors contributed equally to this work.

§§ A McNair Scholar of the Baylor College of Medicine Medical Scientist Training Program.

Supported by National Institutes of Health Grant F32MH65766.

|| Supported by National Institutes of Health Training Grant T32GM8507.

{ddagger}{ddagger} To whom correspondence should be addressed: Division of Neuroscience, Baylor College of Medicine, Houston, TX 77030. Tel.: 713-798-5392; Fax: 713-798-3946; E-mail: rgereau{at}bcm.tmc.edu.


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