Fish Melanocortin System
Ya-Xiong Tao*
Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, Alabama 36849-5519, USA.
Melanocortin system is an ancient system regulating multiple physiological functions in vertebrates, including regulation of pigmentation, adrenal steroidogenesis and cell proliferation, energy and glucose homeostasis, reproductive function, and exocrine gland secretion. It consists of several agonists derived from post-translational processing of a precursor, proopiomelanocortin, two endogenous antagonists (inverse agonists), Agouti-signaling protein and Agouti-related protein, five receptors that bind these ligands termed melanocortin-1 to -5 receptors (MC1R to MC5R). Further, melanocortin receptor accessory proteins (MRAPs) regulate diverse aspects of MCR function, including forward trafficking to the plasma membrane, binding to the ligand, and signaling including both basal and ligand-induced signaling. In this talk, I will summarize the studies on fish melanocortin system, especially in comparison to the mammalian system. Differences in pharmacological properties between fish and mammalian MCRs will be highlighted. For example, we showed that fish MC4Rs have unique properties, including significantly higher constitutive activity compared with human MC4R. They also have very different binding and signaling properties to small molecule ligands developed for human MC4R, suggesting that it is essential to study the pharmacology of the ligands interested for use in aquaculture in fish MC4R. Recent studies on potential roles of MRAPs regulating other G protein-coupled receptors will be highlighted.
Key Words: Melanocortins, proopiomelanocortin, Agouti-signaling protein, Agouti-related protein, melanocortin receptors, melanocortin receptor accessory protein, pharmacology
Ya-Xiong Tao*
Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, Alabama 36849-5519, USA.
Melanocortin system is an ancient system regulating multiple physiological functions in vertebrates, including regulation of pigmentation, adrenal steroidogenesis and cell proliferation, energy and glucose homeostasis, reproductive function, and exocrine gland secretion. It consists of several agonists derived from post-translational processing of a precursor, proopiomelanocortin, two endogenous antagonists (inverse agonists), Agouti-signaling protein and Agouti-related protein, five receptors that bind these ligands termed melanocortin-1 to -5 receptors (MC1R to MC5R). Further, melanocortin receptor accessory proteins (MRAPs) regulate diverse aspects of MCR function, including forward trafficking to the plasma membrane, binding to the ligand, and signaling including both basal and ligand-induced signaling. In this talk, I will summarize the studies on fish melanocortin system, especially in comparison to the mammalian system. Differences in pharmacological properties between fish and mammalian MCRs will be highlighted. For example, we showed that fish MC4Rs have unique properties, including significantly higher constitutive activity compared with human MC4R. They also have very different binding and signaling properties to small molecule ligands developed for human MC4R, suggesting that it is essential to study the pharmacology of the ligands interested for use in aquaculture in fish MC4R. Recent studies on potential roles of MRAPs regulating other G protein-coupled receptors will be highlighted.
Key Words: Melanocortins, proopiomelanocortin, Agouti-signaling protein, Agouti-related protein, melanocortin receptors, melanocortin receptor accessory protein, pharmacology