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Melatonin receptors and their regulation: biochemical and structural mechanisms.

机译：褪黑激素受体及其调节：生化和结构机制。

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There is growing evidence demonstrating the complexity of melatonin's role in modulating a diverse number of physiological processes. This complexity could be attributed to the fact that melatonin receptors belong to two distinct classes of proteins, that is, the G-protein coupled receptor superfamily (MT(1), MT(2)) and the quinone reductase enzyme family (MT(3)) which makes them unique at the molecular level. Also, within the G-protein coupled receptor family of proteins, the MT(1) and MT(2) receptors can couple to multiple and distinct signal transduction cascades whose activation can lead to unique cellular responses. Also, throughout the 24-hour cycle, the receptors' sensitivity to specific cues fluctuates and this sensitivity can be modulated in a homologous fashion, that is, by melatonin itself, and in a heterologous manner, that is, by other cues including the photoperiod or estrogen. This sensitivity of response may reflect changes in melatonin receptor density that also occurs throughout the 24-hour light/dark cycle but out of phase with circulating melatonin levels. The mechanisms that underlie the changes in melatonin receptor density and function are still not well-understood, but data is beginning to show that transcriptional events and G-protein uncoupling may be involved. Even though this area of research is still in its infancy, great strides are being made everyday in elucidating the mechanisms that underlie melatonin receptor function and regulation. The focus of this review is to highlight some of these discoveries in an attempt to reveal the uniqueness of the melatonin receptor family while at the same time provide thought-provoking ideas to further advance this area of research. Thus, a brief overview of each of the mammalian melatonin receptor subtypes and the signal transduction cascades to which they couple will be discussed with a greater emphasis placed on the mechanisms underlying their regulation and the domains within the receptors essential for proper signaling.
机译：越来越多的证据表明褪黑激素在调节多种生理过程中作用的复杂性。这种复杂性可归因于褪黑激素受体属于两类不同的蛋白质，即G蛋白偶联受体超家族（MT（1），MT（2））和醌还原酶家族（MT（3） ）），使其在分子水平上具有独特性。同样，在蛋白质的G蛋白偶联受体家族中，MT（1）和MT（2）受体可以偶联至多个不同的信号转导级联，其​​激活可导致独特的细胞应答。而且，在整个24小时周期中，受体对特定线索的敏感性会发生波动，并且可以通过同源方式（即褪黑激素本身）和异源方式（即，通过包括光周期在内的其他线索）来调节这种敏感性。或雌激素。这种反应的敏感性可能反映了褪黑激素受体密度的变化，该变化在整个24小时的明/暗周期中也会发生，但与循环褪黑激素水平不同。褪黑激素受体密度和功能变化的基础机制仍未得到很好的理解，但是数据开始表明转录事件和G蛋白解偶联可能参与其中。尽管这一研究领域仍处于起步阶段，但在阐明褪黑激素受体功能和调节基础的机制方面，每天都在取得长足进步。这篇综述的重点是突出这些发现中的一些，以试图揭示褪黑激素受体家族的独特性，同时提供令人深思的想法，以进一步推进这一研究领域。因此，将对每种哺乳动物褪黑激素受体亚型及其偶联的信号转导级联进行简要概述，并将重点放在其调控机制和受体内适当信号传导结构域上。

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