TARP γ-8 glycosylation regulates the surface expression of AMPA receptors.

[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 Tduanyu37 γ-8 promotes surface expression of AMPA receptors; however, how Tduanyu37 γ-8 regulates the expression of AMPA receptors remains unclear. In the present study, we examined the effect of Tduanyu37 glycosylation on AMPA receptor trafficking. We first showed that Tduanyu37 γ-8 is an N-glycosylated protein, which contains two glycosylation sites, Asn53 and Asn56, and compared this with the glycosylation of Tduanyu37 γ-2 and the AMPA receptor auxiliary protein CNIH-2 (cornichon homologue 2). We next examine the effect of Tduanyu37 glycosylation on Tduanyu37 trafficking and also on AMPA receptor surface expression. We find that Tduanyu37 γ-8 glycosylation is critical for surface expression of both Tduanyu37 γ-8 and GluA1 in heterologous cells and neurons. Specifically, knockdown of Tduanyu37 γ-8 causes a decrease in both total and surface AMPA receptors. We find that the expression of unglycosylated Tduanyu37 γ-8 in cultured neurons is unable to restore GluA1 expression fully. Furthermore, when the maturation of Tduanyu37 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 Tduanyu37 γ-8 in the trafficking and function of the AMPA receptor complex.

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