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研究揭示机体调控星形细胞抑制的化学遗传学
2020-11-14 23:35

美国杜克大学医学院Scott H. Soderling、Tetsuya Takano和Cagla Eroglu研究组的最新研究揭示了机体调控星形细胞抑制的化学遗传学。 该研究于2020年11月11日发表于国际学术期刊《自然》杂志。

研究人员使用基于细胞表面片段互补策略Split-TurboID的体内化学遗传学方法,鉴定了在体内星形胶质细胞-神经元连接处富集的蛋白质组,其中包括神经元细胞粘附因子(NRCAM)。 研究发现,NRCAM在皮质星形胶质细胞中表达,其定位于突触周围的接触面,并需要通过星形胶质细胞活化过程来限制神经纤维的浸润。

此外,研究表明星形胶质细胞NRCAM在抑制性突触后与gephyrin偶联神经元的NRCAM跨细胞相互作用。星形细胞NRCAM的敲除减少了抑制性突触的数量,而没有改变谷氨酸能突触的密度。并且,星形细胞NRCAM的缺失显著降低了抑制性突触的功能,对兴奋性突触的影响较小。

因此,该研究结果为星形胶质细胞与神经元的相互作用提供了蛋白质组学框架,并揭示了星形胶质细胞如何控制GABAergic突触的形成和功能。

据悉,突触周围的星形细胞是中枢神经系统突触的组成部分; 然而,尚不清楚调控星形胶质细胞-突触粘附的分子机制以及星形胶质细胞接触如何控制突触形成和功能。

附:英文原文

Title: Chemico-genetic discovery of astrocytic control of inhibition in vivo

Author: Tetsuya Takano, John T. Wallace, Katherine T. Baldwin, Alicia M. Purkey, Akiyoshi Uezu, Jamie L. Courtland, Erik J. Soderblom, Tomomi Shimogori, Patricia F. Maness, Cagla Eroglu, Scott H. Soderling

Issue&Volume: 2020-11-11

Abstract: Perisynaptic astrocytic processes are an integral part of central nervous system synapses1,2; however, the molecular mechanisms that govern astrocyte–synapse adhesions and how astrocyte contacts control synapse formation and function are largely unknown. Here we use an in vivo chemico-genetic approach that applies a cell-surface fragment complementation strategy, Split-TurboID, and identify a proteome that is enriched at astrocyte–neuron junctions in vivo, which includes neuronal cell adhesion molecule (NRCAM). We find that NRCAM is expressed in cortical astrocytes, localizes to perisynaptic contacts and is required to restrict neuropil infiltration by astrocytic processes. Furthermore, we show that astrocytic NRCAM interacts transcellularly with neuronal NRCAM coupled to gephyrin at inhibitory postsynapses. Depletion of astrocytic NRCAM reduces numbers of inhibitory synapses without altering glutamatergic synaptic density. Moreover, loss of astrocytic NRCAM markedly decreases inhibitory synaptic function, with minor effects on excitation. Thus, our results present a proteomic framework for how astrocytes interface with neurons and reveal how astrocytes control GABAergic synapse formation and function.

DOI: 10.1038/s41586-020-2926-0

Source: https://www.nature.com/articles/s41586-020-2926-0

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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