Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2008) 15 OC6

SFEBES2008 Oral Communications Young Endocrinologist prize session (8 abstracts)

MRAP2 permits the functional expression of the melanocortin-2-receptor: a new member of a new family of melanocortin receptor accessory proteins

Li Chan 1 , Louise Metherell 1 , Maurice Elphick 2 , J Paul Chapple 1 & Adrian Clark 1


1WHRI, Barts and the London Medical School, QMUL, London, UK; 2School of Biological and Chemical Sciences, QMUL, London, UK.


Background: The identification of MRAP in 2005 as the first melanocortin-2-receptor (MC2R)/ACTH receptor accessory protein provided insight into the regulation of the melanocortin receptor system. Mutations in MRAP cause Familial glucocorticoid deficiency, an autosomal recessive disorder resulting in isolated cortisol deficiency. In vitro studies showed that MRAP was essential for the functional expression of the MC2R. The melanocortin receptor (MCR) family (MC1R to MC5R) are involved in a wide range of physiological and disease processes. MRAP2 is a conserved homologue of MRAP. We therefore hypothesised that MRAP2 was an MCR accessory protein important in the functional expression of one or more of the MCRs.

Aims: To determine the tissue distribution of MRAP2 and characterise the protein and its interactions with other the MCRs.

Results: RT-PCR revealed expression of MRAP2 in the brain and adrenal in humans. On heterologous expression MRAP2 is localised to the cell surface and the endoplasmic reticulum. The MRAP2-FLAG protein is ~27 and 29 kDa. The 29 kDa isoform is a glycosylated form as treatment with endoglycosidases and/or mutagenesis of the putative N-glycosylation site resulted in its disappearance. Co-immunoprecipitation studies demonstrated that MRAP2 interacts with the MC2R, homodimerises and can heterodimerise with MRAP. MRAP2 enhances the cell surface expression of the MC2R in transfected cells and enables signalling of the MC2R and cAMP generation in response to ACTH.

Discussion: This is the first study demonstrating the importance of MRAP2 in the functional expression of the MC2R. MRAP2 therefore joins MRAP in a new melanocortin accessory protein family. The interplay between these 2 small transmembrane proteins on MC2R function may provide further insight to melanocortin receptor regulation.

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