Alberto J Gonzalez-Hernandez, Hermany Munguba, Joshua Levitz
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引用次数: 0
摘要
在神经系统中,G 蛋白偶联受体(GPCR)通过在时空上精确启动各种信号通路,控制神经元的兴奋性、突触传递、突触可塑性,并最终控制行为。然而,尽管这些受体至关重要,但人们对它们是如何根据特定的神经生理环境调节信号传递的了解却并不全面。我们需要对神经调节 GPCR 的功能进行更深入的机理研究,以全面解读它们的生物学作用,并有效地利用它们来治疗神经和精神疾病。在这篇综述中,我们将重点介绍最近在确定神经调节 GPCR 的新型调控模式方面取得的进展,包括 G 蛋白和受体靶向机制、受体与受体之间的串扰以及在化学突触背景下出现的独特特征。这些新出现的神经调节 GPCR 调控原理提出了未来需要在分子、细胞、突触和神经回路层面解决的关键问题。
Emerging modes of regulation of neuromodulatory G protein-coupled receptors.
In the nervous system, G protein-coupled receptors (GPCRs) control neuronal excitability, synaptic transmission, synaptic plasticity, and, ultimately, behavior through spatiotemporally precise initiation of a variety of signaling pathways. However, despite their critical importance, there is incomplete understanding of how these receptors are regulated to tune their signaling to specific neurophysiological contexts. A deeper mechanistic picture of neuromodulatory GPCR function is needed to fully decipher their biological roles and effectively harness them for the treatment of neurological and psychiatric disorders. In this review, we highlight recent progress in identifying novel modes of regulation of neuromodulatory GPCRs, including G protein- and receptor-targeting mechanisms, receptor-receptor crosstalk, and unique features that emerge in the context of chemical synapses. These emerging principles of neuromodulatory GPCR tuning raise critical questions to be tackled at the molecular, cellular, synaptic, and neural circuit levels in the future.
期刊介绍:
For over four decades, Trends in Neurosciences (TINS) has been a prominent source of inspiring reviews and commentaries across all disciplines of neuroscience. TINS is a monthly, peer-reviewed journal, and its articles are curated by the Editor and authored by leading researchers in their respective fields. The journal communicates exciting advances in brain research, serves as a voice for the global neuroscience community, and highlights the contribution of neuroscientific research to medicine and society.