Melanocortins are known to be involved in the regulation of feeding behavior. These hormones mediate their effects through G protein-coupled receptors (GPCRs) by stimulating adenylate cyclase. The melanocortin 3 receptor (MC3R) in the melanocortin receptor (MCR) family has been identified as a neural receptor subtype mainly expressed in the brain in mammals. Until now, only one heterozygous mutation (I183N) has been identified in the coding region of this receptor in two obese patients of the same family. In this study, we reported the functional characterization of the I183N mutated MC3R compared with that of the wild-type MC3R after transfection in HEK293 cells. Our results showed that the I183N mutation totally abolished the activity of the mutated receptor to generate intracellular cAMP. Furthermore, confocal microscopy observation revealed that the mutation induced an intracellular retention of the mutated receptor. Moreover, we demonstrated for the first time by co-transfection studies that the mutated receptor could reduce the wild-type receptor activity through a dominant negative effect. © 2004 Elsevier B.V. All rights reserved.
Rached, M., Buronfosse, A., Begeot, M., & Penhoat, A. (2004). Inactivation and intracellular retention of the human I183N mutated melanocortin 3 receptor associated with obesity. Biochimica et Biophysica Acta - Molecular Basis of Disease, 1689(3), 229–234. https://doi.org/10.1016/j.bbadis.2004.03.009