Department of Experimental Biology, Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal Instituto de Biologia Molecular e Celular (IBMC), University of Porto, Porto, Portugal IPATIMUP, Institute of Molecular Pathology and Immunology Faculty of Nutrition and Food Sciences, University of Porto, Porto, Portugal.
J Mol Endocrinol. 2013 Sep 10;51(2):R23-32. doi: 10.1530/JME-13-0055. Print 2013 Oct.
Melanocortin receptors (MCRs) belong to the G-protein-coupled receptor family of transmembrane proteins. They recognize specific ligands named melanocortins that are mainly produced in the pituitary and hypothalamus. Newly synthesized MCRs at the endoplasmic reticulum are subjected to quality control mechanisms that screen for the correct structure, folding or processing, essential for their proper cell surface expression. Some motifs, located at the N- or C-terminus or even on transmembrane and in loop regions, have been implicated in these biological processes. This article reviews these specific domains and the role of accessory proteins and post-translation modifications in MCRs' targeting to cell surface. Additionally, promising approaches involving pharmacological stabilization of misfolded and misrouted mutant MCRs, which improve their forward transport, are reported. Understanding the MCRs' structural determinants fundamental for their proper cell surface integration is essential for correcting abnormalities found in some diseases.
黑素皮质素受体（MCRs）属于 G 蛋白偶联受体家族的跨膜蛋白。它们识别特定的配体，称为黑素皮质素，主要在垂体和下丘脑产生。在内质网上新合成的 MCR 受到质量控制机制的筛选，这些机制筛选出正确的结构、折叠或加工，这对于它们在细胞表面的适当表达是必不可少的。一些位于 N 端或 C 端或甚至在跨膜区和环区的基序，已被牵连到这些生物过程中。本文综述了这些特定的结构域以及辅助蛋白和翻译后修饰在 MCRs 靶向细胞表面过程中的作用。此外，还报道了一些有前途的方法，涉及到对错误折叠和错误途径的突变 MCRs 的药理学稳定化，从而改善它们的正向转运。理解 MCRs 正确细胞表面整合的结构决定因素对于纠正某些疾病中发现的异常是至关重要的。
