title: N-glycosylation of the human melanocortin 1 receptor: occupancy of glycosylation sequons and functional role.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, University of Murcia, Murcia, Spain.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Herraiz
authors.forename: Berta L
authors.initials: BL
authors.lastname: Sánchez-Laorden
authors.forename: Celia
authors.initials: C
authors.lastname: Jiménez-Cervantes
authors.forename: José C
authors.initials: JC
authors.lastname: García-Borrón
mesh_terms: D000818:Animals; D016466:CHO Cells; D049109:Cell Proliferation; D006224:Cricetinae; D003412:Cricetulus; D006031:Glycosylation; D057809:HEK293 Cells; D006801:Humans; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics / Q000378:metabolism*; D012880:Skin Pigmentation; D000521:alpha-MSH / Q000235:genetics / Q000378:metabolism*
chemical_list: D044102:Receptor, Melanocortin, Type 1; D000521:alpha-MSH