A primate-dominant third glycosylation site of the beta2-adrenergic receptor routes receptors to degradation during agonist regulation
Abstract
beta(2)-adrenergic receptors (beta(2)AR) of all species are N-linked glycosylated at amino terminus residues approximately 6 and approximately 15. However, the human beta(2)AR has a potential third N-glycosylation site at ECL2 residue 187. To determine whether this residue is glycosylated and to ascertain function, all possible single/multiple Asn --> Gln mutations were made in the human beta(2) AR at positions 6, 15, and 187 and were expressed in Chinese hamster fibroblast cells. Substitution of Asn-187 alone or with Asn-6 or Asn-15 decreased the apparent molecular mass of the receptor on SDS-PAGE in a manner consistent with Asn-187 glycosylation. All receptors bound the agonist isoproterenol and functionally coupled to adenylyl cyclase. However, receptors without 187 glycosylation failed to display long term agonist-promoted down-regulation. In contrast, loss of Asn-6/Asn-15 glycosylation did not alter down-regulation. Cell surface distribution and agonist-promoted internalization of receptors and recruitment of beta-arrestin 2 were unaffected by the loss of 187 glycosylation. Furthermore, acutely internalized wild-type and Gln-187 receptors were both localized by confocal microscopy to early endosomes. During prolonged agoni...Continue Reading
References
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The h-P2X3 glycoprotein receptor as an example of integrating bioinformatics and structural research
N-glycosylation of the β2 adrenergic receptor regulates receptor function by modulating dimerization
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