TARP [transmembrane AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor regulatory protein] γ-8 is an auxiliary subunit of AMPA receptors that is widely distributed in the hippocampus. It has been shown that TARP γ-8 promotes surface expression of AMPA receptors; however, how TARP γ-8 regulates the expression of AMPA receptors remains unclear. In the present study, we examined the effect of TARP glycosylation on AMPA receptor trafficking. We first showed that TARP γ-8 is an N-glycosylated protein, which contains two glycosylation sites, Asn53 and Asn56, and compared this with the glycosylation of TARP γ-2 and the AMPA receptor auxiliary protein CNIH-2 (cornichon homologue 2). We next examine the effect of TARP glycosylation on TARP trafficking and also on AMPA receptor surface expression. We find that TARP γ-8 glycosylation is critical for surface expression of both TARP γ-8 and GluA1 in heterologous cells and neurons. Specifically, knockdown of TARP γ-8 causes a decrease in both total and surface AMPA receptors. We find that the expression of unglycosylated TARP γ-8 in cultured neurons is unable to restore GluA1 expression fully. Furthermore, when the maturation of TARP γ-8 is impaired, a large pool of immature GluA1 is retained intracellularly. Taken together, our data reveal an important role for the maturation of TARP γ-8 in the trafficking and function of the AMPA receptor complex.
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Research Article|
January 22 2015
TARP γ-8 glycosylation regulates the surface expression of AMPA receptors
Chan-Ying Zheng;
Chan-Ying Zheng
*Receptor Biology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, U.S.A.
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Kai Chang;
Kai Chang
*Receptor Biology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, U.S.A.
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Young Ho Suh;
Young Ho Suh
1
†Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, South Korea
1Correspondence may be addressed to either of these authors (email suhyho@snu.ac.kr or rochek@ninds.nih.gov).
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Katherine W. Roche
Katherine W. Roche
1
*Receptor Biology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, U.S.A.
1Correspondence may be addressed to either of these authors (email suhyho@snu.ac.kr or rochek@ninds.nih.gov).
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Publisher: Portland Press Ltd
Received:
June 27 2014
Revision Received:
October 13 2014
Accepted:
December 11 2014
Accepted Manuscript online:
December 11 2014
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2015 Biochemical Society
2015
Biochem J (2015) 465 (3): 471–477.
Article history
Received:
June 27 2014
Revision Received:
October 13 2014
Accepted:
December 11 2014
Accepted Manuscript online:
December 11 2014
Citation
Chan-Ying Zheng, Kai Chang, Young Ho Suh, Katherine W. Roche; TARP γ-8 glycosylation regulates the surface expression of AMPA receptors. Biochem J 1 February 2015; 465 (3): 471–477. doi: https://doi.org/10.1042/BJ20140806
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