Distinct melanocortin 2 receptor accessory protein domains are required for melanocortin 2 receptor interaction and promotion of receptor trafficking.
Melanocortin 2 receptor (MC2R) is the receptor for the pituitary hormone 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 characterization 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.
Webb
Tom R
TR
Centre for Endocrinology, William Harvey Research Institute, Barts and the London, London, UK.
Chan
Li
L
Cooray
Sadani N
SN
Cheetham
Michael E
ME
Chapple
J Paul
JP
Clark
Adrian J L
AJ
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D016466:CHO Cells; D017124:Conserved Sequence / Q000502:physiology; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D044103:Receptor, Melanocortin, Type 2 / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014162:Transfection
D000954:Antigens, Surface; C458099:MRAP protein, human; D008565:Membrane Proteins; D044103:Receptor, Melanocortin, Type 2; D000324:Adrenocorticotropic Hormone