Regulation of Melanocortin-4 Receptor Pharmacology by Two Isoforms of Melanocortin Receptor Accessory Protein 2 in Topmouth Culter (Culter alburnus)

Frontiers in Endocrinology

Ting Liu¹  Min Tao¹  Ya-Xiong Tao¹  Ren-Lei Ji¹  Si-Yu Fan²  Shao-Jun Liu²  Lu Huang² 

[1] Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL, United States;State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Sciences, Hunan Normal University, Changsha, China;

关键词: topmouth culter;    melanocortin-4 receptor;    melanocortin receptor accessory protein 2;    signaling;    constitutive activity;   

DOI  :  10.3389/fendo.2020.00538

来源: DOAJ

【 摘 要 】

Melanocortin-4 receptor (MC4R) plays important roles in regulation of multiple physiological processes, and interaction of MC4R and melanocortin receptor accessory protein 2 (MRAP2) is suggested to play pivotal role in energy balance of vertebrates. Topmouth culter (Culter alburnus) is an economically important freshwater fish in China. Herein we cloned culter mc4r, mrap2a, and mrap2b. Culter mc4r consisted of a 981 bp open reading frame encoding a protein of 326 amino acids. qRT-PCR revealed that mc4r, mrap2a, and mrap2b were primarily expressed in the central nervous system. In the periphery, mc4r and mrap2b were expressed more widely in the male, while mrap2a was expressed more widely in the female. Culter MC4R could bind to four peptide agonists and increase intracellular cAMP production dose dependently. Culter MC4R was constitutively active in both cAMP and ERK1/2 pathways, which was differentially regulated by culter MRAP2a and MRAP2b. Culter MRAP2a significantly increased Bmax and decreased agonist-stimulated cAMP, while MRAP2b increased cell surface and total expression but did not affect Bmax and agonist-stimulated cAMP. These results will aid the investigation of the potential physiological processes that MC4R might be involved in topmouth culter.

【 授权许可】

Unknown