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N‐glycosylation of the human melanocortin 1 receptor: occupancy of glycosylation sequons and functional role
Author(s) -
Herraiz Cecilia,
SánchezLaorden Berta L.,
JiménezCervantes Celia,
GarcíaBorrón José C.
Publication year - 2011
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/j.1755-148x.2011.00848.x
Subject(s) - glycosylation , melanocortin 1 receptor , n linked glycosylation , receptor , glycan , glycoprotein , internalization , melanocortin , biochemistry , biology , g protein coupled receptor , microbiology and biotechnology , chemistry , gene , phenotype
Summary The melanocortin 1 receptor (MC1R), a major determinant of skin pigmentation and phototype, mediates the actions of α‐melanocyte‐stimulating hormone on melanocytes and is critical for melanocyte proliferation and differentiation. MC1R has two putative N‐glycosylation targets, Asn15 and Asn29. It has been shown that MC1R is a glycoprotein with an unusual sensitivity to endoglycosidase H digestion. However, the occupancy and functional importance of each specific glycosylation sequon remains unknown. We demonstrate that MC1R is N‐glycosylated at Asn15 and Asn29, with structurally and functionally different glycan chains. N‐glycosylation is not necessary for high affinity agonist binding or functional coupling but has a strong effect on the availability of MC1R molecules on the plasma membrane, most likely by a combination of improved forward trafficking and decreased internalization. Finally, we found that MC1R variants exhibit different degrees of glycosylation which do not show a simple correlation with their functional status or intracellular trafficking.