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J. Biol. Chem., Vol. 279, Issue 2, 1408-1414, January 9, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/2/1408    most recent M308656200v1 Alert me when this article is cited 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jin, P. Articles by Fu, G. K. Search for Related Content PubMed PubMed Citation Articles by Jin, P. Articles by Fu, G. K. Social Bookmarking                      What's this?

Cloning and Characterization of a GABA_A Receptor ₂ Subunit Variant^*

Pei Jin, Juan Zhang, Courtney Rowe-Teeter, Junming Yang, Laura L. Stuve, and Glenn K. Fu

From the Incyte Corporation, Palo Alto, California 94304

We have cloned a novel -aminobutyric acid type A (GABA_A) receptor ₂ subunit variant named ₂XL. ₂XL contains an alternatively spliced exon, resulting in the addition of 40 amino acids to the N-terminal extracellular domain between Ser¹⁷¹ and Tyr¹⁷². We show that ₂XL failed to localize to the cell surface when it was coexpressed with the ₂ and ₁ subunits in human embryonic kidney 293 cells. Expression of ₂XL in 293 cells suppressed GABA_A receptor binding in a dose-dependent manner by preventing GABA_A receptor cell-surface localization. We also generated a ₂ mutant with Ser¹⁷¹ and Tyr¹⁷² converted to glycine and threonine, respectively. We demonstrate that this mutant has a significantly lower affinity for the ₂ and ₁ subunits and failed to reach the cell surface when coexpressed with these subunits. Together, our results indicate that Ser¹⁷¹ and Tyr¹⁷² in the ₂ subunit constitute a critical motif. When this motif is disrupted by insertion of the alternative exon, access of the ₂ subunit to the cell surface is prevented.

Received for publication, August 6, 2003 , and in revised form, October 13, 2003.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) CD014120.

^* 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.

To whom correspondence should be addressed: Incyte Corp., 3160 Porter Dr., Palo Alto, CA 94304. Tel.: 650-621-8639; Fax: 650-845-4664; E-mail: pjin{at}incyte.com.

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