TARP {gamma}-8 glycosylation regulates the surface expression of AMPA receptors

Transmembrane AMPA receptor regulatory protein (TARP) 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 show that TARP γ-8 is an N-glycosylated protein, which contains two glycosylation sites, Asn-53 and Asn-56, and compare this to the glycosylation of TARP γ-2 and the AMPAR auxiliary protein, CNIH2. 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.
Source: BJ Cell - Category: Biochemistry Authors: Tags: BJ Cell Source Type: research