Abstract：
The 5 known melanocortin receptors (MCs) have established physiological roles. With the exception of MC2, these receptors can behave unpredictably, and since they are more widely expressed than their established roles would suggest, it is likely that they have other poorly characterized functions. The aim of this review is to discuss some of the less well-explored aspects of the 4 enigmatic members of this receptor family (MC1,3-5) and describe how these are multifaceted G protein-coupled receptors (GPCRs). These receptors appear to be promiscuous in that they bind several endogenous agonists (products of the proopiomelanocortin [POMC] gene) and antagonists but with inconsistent relative affinities and effects. We propose that this is a result of posttranslational modifications that determine receptor localization within nanodomains. Within each nanodomain there will be a variety of proteins, including ion channels, modifying proteins, and other GPCRs, that can interact with the MCs to alter the availability of receptor at the cell surface as well as the intracellular signaling resulting from receptor activation. Different combinations of interacting proteins and MCs may therefore give rise to the complex and inconsistent functional profiles reported for the MCs. For further progress in understanding this family, improved characterization of tissue-specific functions is required. Current evidence for interactions of these receptors with a range of partners, resulting in modulation of cell signaling, suggests that each should be studied within the full context of their interacting partners. The role of physiological status in determining this context also remains to be characterized.
摘要：
已知的黑皮质素受体(MC)已经确立了生理作用。除MC2外，这些受体的行为不可预测，由于他们的表达比他们既定的角色所暗示的更广泛，它们很可能还有其他特征不佳的功能。这篇综述的目的是讨论该受体家族（MC1,3-5）的4个神秘成员的一些不太深入的方面，并描述这些是如何多方面的G蛋白偶联受体（GPCRs）。这些受体似乎是混杂的，因为它们结合了几种内源性激动剂（原黑皮素[POMC]基因的产物）和拮抗剂，但具有不一致的相对亲和力和作用。我们认为这是翻译后修饰的结果，这些修饰决定了受体在纳米域内的定位。在每个纳米域内将有多种蛋白质，包括离子通道，修饰蛋白质，和其他GPCRs，可以与MC相互作用以改变细胞表面受体的可用性以及由受体激活引起的细胞内信号传导。因此,相互作用蛋白和MC的不同组合可产生针对MC报道的复杂且不一致的功能概况。为了进一步了解这个家庭，需要改善组织特异性功能的表征。目前这些受体与一系列伴侣相互作用的证据，导致细胞信号的调节，建议每个人都应该在他们互动伙伴的完整背景下进行研究。生理状态在确定这种情况中的作用也仍有待表征。
