Document Detail


Melanocortin receptor accessory proteins in adrenal gland physiology and beyond.
MedLine Citation:
PMID:  23418361     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The melanocortin receptor (MCR) family consists of five G-protein-coupled receptors (MC1R-MC5R) with diverse physiological roles. MC1R controls pigmentation, MC2R is a critical component of the hypothalamic-pituitary-adrenal axis, MC3R and MC4R have a vital role in energy homeostasis and MC5R is involved in exocrine function. The melanocortin receptor accessory protein (MRAP) and its paralogue MRAP2 are small single-pass transmembrane proteins that have been shown to regulate MCR expression and function. In the adrenal gland, MRAP is an essential accessory factor for the functional expression of the MC2R/ACTH receptor. The importance of MRAP in adrenal gland physiology is demonstrated by the clinical condition familial glucocorticoid deficiency, where inactivating MRAP mutations account for ∼20% of cases. MRAP is highly expressed in both the zona fasciculata and the undifferentiated zone. Expression in the undifferentiated zone suggests that MRAP could also be important in adrenal cell differentiation and/or maintenance. In contrast, the role of adrenal MRAP2, which is highly expressed in the foetal gland, is unclear. The expression of MRAPs outside the adrenal gland is suggestive of a wider physiological purpose, beyond MC2R-mediated adrenal steroidogenesis. In vitro, MRAPs have been shown to reduce surface expression and signalling of all the other MCRs (MC1,3,4,5R). MRAP2 is predominantly expressed in the hypothalamus, a site that also expresses a high level of MC3R and MC4R. This raises the intriguing possibility of a CNS role for the MRAPs.
Authors:
T V Novoselova; D Jackson; D C Campbell; A J L Clark; L F Chan
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review     Date:  2013-03-19
Journal Detail:
Title:  The Journal of endocrinology     Volume:  217     ISSN:  1479-6805     ISO Abbreviation:  J. Endocrinol.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-03-20     Completed Date:  2013-05-06     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  0375363     Medline TA:  J Endocrinol     Country:  England    
Other Details:
Languages:  eng     Pagination:  R1-11     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adrenal Glands / embryology,  metabolism*
Animals
Carrier Proteins / chemistry,  metabolism*
Gene Expression Regulation
Humans
Hypothalamus / metabolism
Membrane Proteins / chemistry,  metabolism*
Nerve Tissue Proteins / biosynthesis,  chemistry,  metabolism
Neurons / metabolism
Receptors, Melanocortin / biosynthesis,  chemistry,  metabolism
Grant Support
ID/Acronym/Agency:
G0802796//Medical Research Council
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/MRAP protein, human; 0/MRAP2 protein, human; 0/Membrane Proteins; 0/Nerve Tissue Proteins; 0/Receptors, Melanocortin

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