Role of N-glycan-dependent quality control in the cell-surface expression of the AT1 receptor

Most G protein-coupled receptors (GPCRs) are N-glycosylated proteins but the role of this post-translational modification in GPCR biosynthesis has not been extensively studied. We previously showed that the non-glycosylated AT1 receptor is inefficiently expressed at the cell surface. In this study, we addressed whether AT1 interacts with elements of the ER-based quality control processes. Interestingly, non-glycosylated AT1 receptors associated with the molecular chaperones calnexin and HSP70, suggesting the importance of protein-based interactions between these partners. We also demonstrate that ER mannosidase I participates in the acquisition of mature glycoforms and in the targeting of the AT1 receptor to the membrane. Taken together, these results indicate that decreased cell-surface expression of the non-glycosylated receptor cannot be attributed to diminished interactions with molecular chaperones and that mannose trimming of the wild-type AT1 receptor by ER mannosidase I plays a critical role in its cell-surface expression.