Institut de Génomique Fonctionnelle, Université de Montpellier, CNRS, INSERM, 34094 Montpellier, France.
Cells. 2023 Jan 27;12(3):426. doi: 10.3390/cells12030426.
The serotonin (5-HT) receptor still raises particular interest given its unique spatio-temporal pattern of expression among the serotonin receptor subtypes. It is the only serotonin receptor specifically expressed in the central nervous system, where it is detected very early in embryonic life and modulates key neurodevelopmental processes, from neuronal migration to brain circuit refinement. Its predominant localization in the primary cilium of neurons and astrocytes is also unique among the serotonin receptor subtypes. Consistent with the high expression levels of the 5-HT receptor in brain regions involved in the control of cognitive processes, it is now well-established that the pharmacological inhibition of the receptor induces pro-cognitive effects in several paradigms of cognitive impairment in rodents, including models of neurodevelopmental psychiatric disorders and neurodegenerative diseases. The 5-HT receptor can engage several signaling pathways in addition to the canonical Gs signaling, but there is still uncertainty surrounding the signaling pathways that underly its modulation of cognition, as well as how the receptor's coupling is dependent on its cellular compartmentation. Here, we describe recent findings showing how the proper subcellular localization of the receptor is achieved, how this peculiar localization determines signaling pathways engaged by the receptor, and their pathophysiological influence.
血清素（5-HT）受体仍然引起了特别的关注，因为它在血清素受体亚型中具有独特的时空表达模式。它是唯一在中枢神经系统中特异性表达的血清素受体，在胚胎生命早期就可以检测到，并且调节关键的神经发育过程，从神经元迁移到大脑回路细化。它在神经元和星形胶质细胞的初级纤毛中的主要定位在血清素受体亚型中也是独特的。与 5-HT 受体在参与认知过程控制的大脑区域中的高表达水平一致，现在已经确立，在几种认知障碍的啮齿动物模型中，包括神经发育性精神障碍和神经退行性疾病的模型，该受体的药理学抑制会诱导认知前效应。5-HT 受体除了经典的 Gs 信号外，还可以参与几种信号通路，但对于其调节认知的信号通路以及受体的偶联如何依赖于其细胞区室化，仍然存在不确定性。在这里，我们描述了最近的发现，这些发现表明了受体如何实现适当的亚细胞定位，这种特殊的定位如何决定受体所涉及的信号通路，以及它们的病理生理影响。
