The Melanocortin Receptor Accessory Protein 2 promotes food intake through inhibition of the Prokineticin Receptor-1

Chaly, Anna L; Srisai, Dollada; Gardner, Ellen E; Sebag, Julien A.

doi:10.7554/elife.12397

Cited by 72 publications

(102 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The actual role of MRAP in the modulation of MC3R-regulated food intake and body weight, however, is still up for debate. Recently, MRAP2 has also been demonstrated to play a role in the function of the prokineticin-1 and -2 receptors, suggesting this protein may be a modulator of multiple GPCRs (Chaly et al 2016), and exert effects on feeding and body weight through multifactorial effects.…”

Section: Pharmacological Complexities Of α-Msh Signalingmentioning

confidence: 99%

60 YEARS OF POMC: Regulation of feeding and energy homeostasis by α-MSH

Anderson

Çakır

Carrington

et al. 2016

Journal of Molecular Endocrinology

126

117

View full text Add to dashboard Cite

The melanocortin peptides derived from pro-opiomelanocortin (POMC) were originally understood in terms of the biological actions of α-melanocyte-stimulating hormone (α-MSH) on pigmentation and adrenocorticotrophic hormone on adrenocortical glucocorticoid production. However, the discovery of POMC mRNA and melanocortin peptides in the CNS generated activities directed at understanding the direct biological actions of melanocortins in the brain. Ultimately, discovery of unique melanocortin receptors expressed in the CNS, the melanocortin-3 (MC3R) and melanocortin-4 (MC4R) receptors, led to the development of pharmacological tools and genetic models leading to the demonstration that the central melanocortin system plays a critical role in the regulation of energy homeostasis. Indeed, mutations in MC4R are now known to be the most common cause of early onset syndromic obesity, accounting for 2–5% of all cases. This review discusses the history of these discoveries, as well as the latest work attempting to understand the molecular and cellular basis of regulation of feeding and energy homeostasis by the predominant melanocortin peptide in the CNS, α-MSH.

show abstract

Section: Pharmacological Complexities Of α-Msh Signalingmentioning

confidence: 99%

60 YEARS OF POMC: Regulation of feeding and energy homeostasis by α-MSH

Anderson

Çakır

Carrington

et al. 2016

Journal of Molecular Endocrinology

126

117

View full text Add to dashboard Cite

show abstract

“…As with MRAP, MRAP2 also naturally exists as an antiparallel homodimer but with a distinct tissue expression pattern principally in many areas of the CNS (Chan et al 2009, Asai et al 2013, Chaly et al 2016. We demonstrated that MRAP2 interacted with all five of the melanocortin receptors in transfected cells (as does MRAP1) (Chan et al 2009).…”

Section: Mrap2mentioning

confidence: 80%

“…More recently, Chaly and coworkers (Chaly et al 2016) reported an interaction between the prokineticin 1 and 2 receptors (PKR1 and PKR2) and MRAP2, and an inhibitory effect of MRAP2 when expressed in vitro with these receptors (although a 10:1 ratio of MRAP2 to PKR1 or PKR2 expression vector was used). These findings are particularly interesting in the light of the Mrap2-knockout mouse studies.…”

Section: Are the Mraps Promiscuous?mentioning

confidence: 99%

Promiscuity among the MRAPs

Clark

Chan

2017

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

The melanocortin 2 receptor accessory protein (MRAP) was originally discovered to be an essential co-receptor for the ACTH receptor/melanocortin 2 receptor, and it physically interacts with this receptor and is required for receptor trafficking and ligand binding. A related molecule, MRAP2, is mainly expressed in the CNS and appears to have a role with the melanocortin 4 receptor. Consistent with this is the observation that a massively obese phenotype develops when the Mrap2 gene is deleted in mice. However, the characteristics of this phenotype differ from those of Mc4r-deleted mice and suggest that an additional role, possibly resulting from an interaction with other receptors is possible. In support of this, a functional interaction with the prokineticin receptors was recently reported. Evidence for other receptor interactions and aspects of the tissue distribution of MRAP and MRAP2 gene expression may indicate that these accessory proteins have a wider role than with the melanocortin receptors alone.

show abstract

“…Recently, PKR1 has been shown as the first non-melanocortin GPCR to be regulated by the melanocortin receptor accessory protein 2 (MRAP2). Indeed, MRAP2 significantly and specifically inhibits PKR1 signaling [16].…”

Section: Prokineticin-2 Is An Anorexigenic Peptidementioning

confidence: 99%

Obesity Peptide: Prokineticin

Nebigil¹

2017

Adiposity - Omics and Molecular Understanding

View full text Add to dashboard Cite

Obesity confers an increased risk for cardiovascular renal diseases, diabetes mellitus, nonalcoholic steatohepatitis, musculoskeletal disorders, and cancers. Prokineticin-2 is a peptide hormone, which exists as both a circulating hormone system and a local paracrine-signaling mechanism within various tissues including the brain, kidney, and adipose. It acts on the G-protein-coupled receptors (GPCRs) PKR1 and PKR2. The role of prokineticin-2 in the central nervous system is the control of food intake. Its anorexigenic effect is at least partly through the hypothalamic melanocortin system. Prokineticin-2 also prevents adipose tissue expansion by limiting preadipocyte proliferation and differentiation capacity. Prokineticin-2 signaling is important for insulin capillary passages. It also regulates heart and kidney development and function. Here, we discuss a new obesity peptide prokineticin signaling in central regulation of food intake, adipocyte tissue development, and cardiovascular function. Prokineticin may play a key role in the association between obesity and cardiovascular diseases. We also outline the potential of prokineticin receptor-1 as target for the treatment of obesity and cardiovascular diseases.

show abstract

The Melanocortin Receptor Accessory Protein 2 promotes food intake through inhibition of the Prokineticin Receptor-1

Cited by 72 publications

References 32 publications

60 YEARS OF POMC: Regulation of feeding and energy homeostasis by α-MSH

60 YEARS OF POMC: Regulation of feeding and energy homeostasis by α-MSH

Promiscuity among the MRAPs

Obesity Peptide: Prokineticin

Contact Info

Product

Resources

About