title: TARP γ-8 glycosylation regulates the surface expression of AMPA receptors.
abstract: 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.
authors.affiliation: *Receptor Biology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, U.S.A.
authors.forename: Chan-Ying
authors.initials: CY
authors.lastname: Zheng
authors.affiliation: *Receptor Biology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, U.S.A.
authors.forename: Kai
authors.initials: K
authors.lastname: Chang
authors.affiliation: †Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, South Korea.
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Suh
authors.affiliation: *Receptor Biology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, U.S.A.
authors.forename: Katherine W
authors.initials: KW
authors.lastname: Roche
mesh_terms: D000818:Animals; D019556:COS Cells; D015220:Calcium Channels / Q000378:metabolism*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D006031:Glycosylation; D057809:HEK293 Cells; D006801:Humans; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000096:biosynthesis*
chemical_list: D015220:Calcium Channels; D018091:Receptors, AMPA; C588152:cacng8 protein, rat