空间与时间的问题：疾病相关蛋白在神经发育中的新兴作用。
A matter of space and time: Emerging roles of disease-associated proteins in neural development.
机构信息
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA, USA.
Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA; Stanford Brain Organogenesis, Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA.
出版信息
Neuron. 2022 Jan 19;110(2):195-208. doi: 10.1016/j.neuron.2021.10.035. Epub 2021 Nov 29.
Recent genetic studies of neurodevelopmental disorders point to synaptic proteins and ion channels as key contributors to disease pathogenesis. Although many of these proteins, such as the L-type calcium channel Ca1.2 or the postsynaptic scaffolding protein SHANK3, have well-studied functions in mature neurons, new evidence indicates that they may subserve novel, distinct roles in immature cells as the nervous system is assembled in prenatal development. Emerging tools and technologies, including single-cell sequencing and human cellular models of disease, are illuminating differential isoform utilization, spatiotemporal expression, and subcellular localization of ion channels and synaptic proteins in the developing brain compared with the adult, providing new insights into the regulation of developmental processes. We propose that it is essential to consider the temporally distinct and cell-specific roles of these proteins during development and maturity in our framework for understanding neuropsychiatric disorders.
最近对神经发育障碍的遗传研究表明，突触蛋白和离子通道是导致疾病发病机制的关键因素。尽管这些蛋白质中的许多，如 L 型钙通道 Ca1.2 或突触后支架蛋白 SHANK3，在成熟神经元中具有很好研究的功能，但新的证据表明，在神经系统在前庭发育中组装时，它们可能在不成熟的细胞中发挥新的、独特的作用。新兴的工具和技术，包括单细胞测序和疾病的人类细胞模型，正在阐明离子通道和突触蛋白在发育中的大脑中的差异异构体利用、时空表达和亚细胞定位与成年大脑相比的情况，为发育过程的调控提供了新的见解。我们提出，在我们理解神经精神疾病的框架中，考虑这些蛋白质在发育和成熟过程中的时间上不同和细胞特异性作用是至关重要的。
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