N-glycosylation of the human melanocortin 1 receptor: occupancy of glycosylation sequons and functional role

• Published in: Pigment cell and melanoma research Vol. 24; no. 3; pp. 479 - 489
• Main Authors: Herraiz, Cecilia, Sánchez-Laorden, Berta L., Jiménez-Cervantes, Celia, García-Borrón, José C.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.06.2011
• Subjects: alpha-MSH - genetics; alpha-MSH - metabolism; Animals; Cell Proliferation; CHO Cells; Cricetinae; Cricetulus; functional coupling; Glycosylation; HEK293 Cells; Humans; MC1R variants; melanocortin 1 receptor; Melanocytes - cytology; Melanocytes - metabolism; N-glycosylation; Protein Transport - physiology; Receptor, Melanocortin, Type 1 - genetics; Receptor, Melanocortin, Type 1 - metabolism; Skin Pigmentation; trafficking
• ISSN: 1755-1471; 1755-148X
• DOI: 10.1111/j.1755-148X.2011.00848.x

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.