Stogsdill Jeff A, Ramirez Juan, Liu Di, Kim Yong Ho, Baldwin Katherine T, Enustun Eray, Ejikeme Tiffany, Ji Ru-Rong, Eroglu Cagla
Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Nature. 2017 Nov 8;551(7679):192-197. doi: 10.1038/nature24638.
Astrocytes are complex glial cells with numerous fine cellular processes that infiltrate the neuropil and interact with synapses. The mechanisms that control the establishment of astrocyte morphology are unknown, and it is unclear whether impairing astrocytic infiltration of the neuropil alters synaptic connectivity. Here we show that astrocyte morphogenesis in the mouse cortex depends on direct contact with neuronal processes and occurs in parallel with the growth and activity of synaptic circuits. The neuroligin family cell adhesion proteins NL1, NL2, and NL3, which are expressed by cortical astrocytes, control astrocyte morphogenesis through interactions with neuronal neurexins. Furthermore, in the absence of astrocytic NL2, the formation and function of cortical excitatory synapses are diminished, whereas inhibitory synaptic function is enhanced. Our findings highlight a previously undescribed mechanism of action for neuroligins and link astrocyte morphogenesis to synaptogenesis. Because neuroligin mutations have been implicated in various neurological disorders, these findings also point towards an astrocyte-based mechanism of neural pathology.
星形胶质细胞是复杂的神经胶质细胞，具有众多细小的细胞突起，这些突起渗透到神经毡并与突触相互作用。控制星形胶质细胞形态形成的机制尚不清楚，并且尚不清楚损害神经毡中星形胶质细胞的浸润是否会改变突触连接性。在这里，我们表明小鼠皮质中的星形胶质细胞形态发生取决于与神经元突起的直接接触，并与突触回路的生长和活动同时发生。皮质星形胶质细胞表达的神经连接蛋白家族细胞粘附蛋白NL1、NL2和NL3通过与神经元神经突触素相互作用来控制星形胶质细胞的形态发生。此外，在没有星形胶质细胞NL2的情况下，皮质兴奋性突触的形成和功能会减弱，而抑制性突触功能会增强。我们的研究结果突出了神经连接蛋白以前未被描述的作用机制，并将星形胶质细胞形态发生与突触发生联系起来。由于神经连接蛋白突变与各种神经系统疾病有关联性, 这些发现也指向了一种基于星形胶质细胞的神经病理学机制。
