Inserm, U1016, Institut Cochin, Paris, France; CNRS UMR 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
Inserm, U1016, Institut Cochin, Paris, France; CNRS UMR 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
Int Rev Cell Mol Biol. 2018;338:59-77. doi: 10.1016/bs.ircmb.2018.02.002. Epub 2018 Apr 5.
The melatonin receptor subfamily is composed of three members, MT and MT, which are binding to melatonin, and GPR50, which shows high sequence homology to MT and MT but does not bind to melatonin or any other known ligand. An interesting feature of these receptors is their capacity to form homo- and heteromers between each other and also with other GPCRs. The following heteromers have been described: MT/MT, MT/GPR50, and heteromers composed of MT and the serotonin 5-HT receptor or the orphan GPR61, GPR62, and GPR135 receptors. These heteromers represent novel pharmacological entities as they exhibit functional properties that are different from those of the corresponding homomers. Formation of several of these heteromers has been confirmed in tissues. MT/5-HT heteromers are targeted by the clinically relevant antidepressant agomelatine, and MT/MT heteromers regulate nocturnal retinal light sensitivity. Here, we resume our current knowledge on melatonin receptor heteromerization and discuss how it contributes to the diversification of the function of melatonin receptors.
褪黑素受体亚家族由三个成员组成，MT 和 MT 与褪黑素结合，GPR50 与 MT 和 MT 具有高度的序列同源性，但不与褪黑素或任何其他已知配体结合。这些受体的一个有趣特征是它们能够在彼此之间以及与其他 GPCR 形成同源和异源二聚体。以下异源二聚体已被描述：MT/MT、MT/GPR50 以及由 MT 和血清素 5-HT 受体或孤儿 GPR61、GPR62 和 GPR135 受体组成的异源二聚体。这些异源二聚体代表新的药理学实体，因为它们表现出不同于相应同源二聚体的功能特性。在组织中已经证实了几种这些异源二聚体的形成。MT/5-HT 异源二聚体是临床相关抗抑郁药阿戈美拉汀的作用靶点，而 MT/MT 异源二聚体调节夜间视网膜光敏感性。在这里，我们总结了我们目前对褪黑素受体异源二聚化的认识，并讨论了它如何有助于褪黑素受体功能的多样化。
