Regulation of melanocortin-1 receptor pharmacology by melanocortin receptor accessory protein 2 in orange-spotted grouper (Epinephelus coioides)

2020 ◽  
Vol 285 ◽  
pp. 113291 ◽  
Author(s):  
Li-Qin Ji ◽  
Ying-Zhu Rao ◽  
Yong Zhang ◽  
Rong Chen ◽  
Ya-Xiong Tao
Keyword(s):  
Melanocortin Receptor ◽  
Accessory Protein ◽  
Epinephelus Coioides ◽  
Melanocortin 1 Receptor ◽  
Receptor Pharmacology ◽  
Receptor Accessory Protein

scholarly journals Melanocortin Receptor Accessory Protein 2-Induced Adrenocorticotropic Hormone Response of Human Melanocortin 4 Receptor

2018 ◽  
Vol 3 (2) ◽  
pp. 314-323 ◽  
Author(s):  
Lucia Soletto ◽  
Sergio Hernández-Balfagó ◽  
Ana Rocha ◽  
Patrick Scheerer ◽  
Gunnar Kleinau ◽  
...  
Keyword(s):  
Adrenocorticotropic Hormone ◽  
Melanocortin Receptor ◽  
Accessory Protein ◽  
Hormone Response ◽  
Melanocortin 4 Receptor ◽  
Receptor Accessory Protein

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

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Anna L Chaly ◽  
Dollada Srisai ◽  
Ellen E Gardner ◽  
Julien A Sebag
Keyword(s):  
Food Intake ◽  
Energy Homeostasis ◽  
Severe Obesity ◽  
Melanocortin Receptor ◽  
Accessory Protein ◽  
Important Regulator ◽  
Receptor Accessory Protein

The Melanocortin Receptor Accessory Protein 2 (MRAP2) is an important regulator of energy homeostasis and its loss causes severe obesity in rodents. MRAP2 mediates its action in part through the potentiation of the MC4R, however, it is clear that MRAP2 is expressed in tissues that do not express MC4R, and that the deletion of MRAP2 does not recapitulate the phenotype of Mc4r KO mice. Consequently, we hypothesized that other GPCRs involved in the control of energy homeostasis are likely to be regulated by MRAP2. In this study we identified PKR1 as the first non-melanocortin GPCR to be regulated by MRAP2. We show that MRAP2 significantly and specifically inhibits PKR1 signaling. We also demonstrate that PKR1 and MRAP2 co-localize in neurons and that Mrap2 KO mice are hypersensitive to PKR1 stimulation. This study not only identifies new partners of MRAP2 but also a new pathway through which MRAP2 regulates energy homeostasis.

Decreased melanocortin-4 receptor function conferred by an infrequent variant at the human melanocortin receptor accessory protein 2 gene

Obesity ◽  
2016 ◽  
Vol 24 (9) ◽  
pp. 1976-1982 ◽  
Author(s):  
Laura Schonnop ◽  
Gunnar Kleinau ◽  
Nikolas Herrfurth ◽  
Anna-Lena Volckmar ◽  
Cigdem Cetindag ◽  
...  
Keyword(s):  
Melanocortin Receptor ◽  
Accessory Protein ◽  
Receptor Function ◽  
Melanocortin 4 Receptor ◽  
Receptor Accessory Protein

scholarly journals Membrane Orientation and Oligomerization of the Melanocortin Receptor Accessory Protein 2

2020 ◽  
Author(s):  
Valerie Chen ◽  
Antonio E. Bruno ◽  
Laura L. Britt ◽  
Ciria C. Hernandez ◽  
Luis E. Gimenez ◽  
...  
Keyword(s):  
Transmembrane Domain ◽  
Membrane Topology ◽  
Melanocortin Receptor ◽  
Accessory Protein ◽  
Metabolic Dysfunction ◽  
Loss Of Function ◽  
Membrane Orientation ◽  
Eukaryotic Proteins ◽  
G Protein Coupled ◽  
Receptor Accessory Protein

ABSTRACTThe melanocortin receptor accessory protein 2 (MRAP2) plays a pivotal role in the regulation of several G-protein coupled receptors (GPCR) that are essential for energy balance and food intake. MRAP2 loss-of-function results in obesity in mammals. MRAP2 and its homolog MRAP1 have an unusual membrane topology and are the only known eukaryotic proteins that thread into the membrane in both orientations. In this study, we demonstrate that the conserved polybasic motif that dictates the membrane topology and dimerization of MRAP1 does not control the membrane orientation and dimerization of MRAP2. We also show that MRAP2 dimerizes through its transmembrane domain and can form higher order oligomers that arrange MRAP2 monomers in a parallel orientation. Investigating the molecular details of MRAP2 structure is essential for understanding the mechanism by which it regulates GPCRs and will aid in elucidating the pathways involved in metabolic dysfunction.

scholarly journals Pharmacological modulation of two melanocortin-5 receptors by MRAP2 proteins in zebrafish

2019 ◽  
Vol 62 (1) ◽  
pp. 27-36 ◽  
Author(s):  
Ming Zhu ◽  
Meng Wang ◽  
Yijun Chen ◽  
Chao Zhang
Keyword(s):  
Surface Expression ◽  
Evolutionary Conservation ◽  
Bimolecular Fluorescence Complementation ◽  
Melanocortin Receptor ◽  
Melanocortin Receptors ◽  
Accessory Protein ◽  
Pharmacological Effects ◽  
Zebrafish Brain ◽  
Pharmacological Modulation ◽  
Receptor Accessory Protein

Melanocortin receptor accessory protein 2 (MRAP2) plays an important role in regulating melanocortin receptors. In zebrafish, MRAP2a and MRAP2b show distinct pharmacological effects on MC4R activity, but how MRAP2 protein regulates other zebrafish melanocortin receptors is barely studied. Zebrafish have two mc5r genes: mc5ra and mc5rb, it is still vague which one is the homologous isoform to the mammalian paralog. Here, we utilize synteny and phylogenetic analysis to demonstrate the evolutionary conservation of zebrafish MC5Ra and MC5Rb among different species. We also show that MRAP2a and MRAP2b could interact and regulate surface expression of two MC5R receptors. Bimolecular fluorescence complementation (BiFC) studies suggest that zebrafish MC5Rs could form homo- and heterodimers, which are suppressed by co-expression with MRAP2 proteins. In comparison with mammalian MC5R-MRAP2 system and different pharmacological effects of zMRAP2 protein on MC5Rs, zmc5ra is identified as the evolutionary homologous paralog to the mammals, and it is regulated by metabolic state in zebrafish brain region.

scholarly journals Membrane orientation and oligomerization of the melanocortin receptor accessory protein 2

2020 ◽  
Vol 295 (48) ◽  
pp. 16370-16379
Author(s):  
Valerie Chen ◽  
Antonio E. Bruno ◽  
Laura L. Britt ◽  
Ciria C. Hernandez ◽  
Luis E. Gimenez ◽  
...  
Keyword(s):  
G Protein ◽  
Transmembrane Domain ◽  
G Protein Coupled Receptors ◽  
Membrane Topology ◽  
Melanocortin Receptor ◽  
Accessory Protein ◽  
Loss Of Function ◽  
Membrane Orientation ◽  
G Protein Coupled ◽  
Receptor Accessory Protein

The melanocortin receptor accessory protein 2 (MRAP2) plays a pivotal role in the regulation of several G protein–coupled receptors that are essential for energy balance and food intake. MRAP2 loss-of-function results in obesity in mammals. MRAP2 and its homolog MRAP1 have an unusual membrane topology and are the only known eukaryotic proteins that thread into the membrane in both orientations. In this study, we demonstrate that the conserved polybasic motif that dictates the membrane topology and dimerization of MRAP1 does not control the membrane orientation and dimerization of MRAP2. We also show that MRAP2 dimerizes through its transmembrane domain and can form higher-order oligomers that arrange MRAP2 monomers in a parallel orientation. Investigating the molecular details of MRAP2 structure is essential for understanding the mechanism by which it regulates G protein–coupled receptors and will aid in elucidating the pathways involved in metabolic dysfunction.

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