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 AT(1) receptor is inefficiently expressed at the cell surface. In this study, we addressed whether AT(1) interacts with elements of the ER-based quality control processes. Interestingly, non-glycosylated AT(1) 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 AT(1) 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 AT(1) receptor by ER mannosidase I plays a critical role in its cell-surface expression.
Lanctôt
Pascal M
PM
Department of Pharmacology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Que., Canada J1H 5N4.
Leclerc
Patrice C
PC
Escher
Emanuel
E
Guillemette
Gaétan
G
Leduc
Richard
R
D000818:Animals; D019556:COS Cells; D037281:Calnexin / Q000378:metabolism / Q000502:physiology; D002236:Carbohydrate Conformation; D002462:Cell Membrane / Q000378:metabolism*; D002522:Chlorocebus aethiops; D004721:Endoplasmic Reticulum / Q000201:enzymology / Q000378:metabolism; D006031:Glycosylation; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007700:Kinetics; D008361:Mannosidases / Q000502:physiology; D011134:Polysaccharides / Q000502:physiology*; D044140:Receptor, Angiotensin, Type 1 / Q000096:biosynthesis / Q000235:genetics*
D018840:HSP70 Heat-Shock Proteins; D011134:Polysaccharides; D044140:Receptor, Angiotensin, Type 1; D037281:Calnexin; D008361:Mannosidases; C046090:mannosyl-oligosaccharide 1,2-alpha-mannosidase