Distinct MRAP domains are required for MC2R interaction and promotion of receptor trafficking

• Published in: Endocrinology (Philadelphia) Vol. 150; no. 2; pp. 720 - 726
• Main Authors: Webb, Tom R., Chan, Li, Cooray, Sadani N., Cheetham, Michael E., Chapple, J. Paul, Clark, Adrian J. L.
• Format: Journal Article
• Language: English
• Published: 25-09-2008
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2008-0941

Melanocortin 2 receptor (MC2R) is the receptor for the pituitary hormone adrenocorticotropin (ACTH). When activated, MC2R stimulates cAMP production and adrenal steroidogenesis. The functional expression of the receptor requires Melanocortin 2 receptor accessory protein (MRAP) a single transmembrane domain protein involved in the trafficking of MC2R from the endoplasmic reticulum to the cell surface. Mutations in both MC2R and MRAP cause the inherited disease Familial Glucocorticoid Deficiency. At present, little is known regarding the mechanism of MRAP in MC2R functional expression. Here we report the characterisation of MRAP in the trafficking of MC2R to the cell surface and the formation of a functional receptor. We identify the transmembrane domain of MRAP as the MC2R interaction domain, and a conserved N-terminal tyrosine rich domain of MRAP that is required for trafficking MC2R to the cell surface.