Laboratory of Molecular Neural Biology, School of Life Sciences, Shanghai University, 99 Shang Da Road, Shanghai 200444, China.
School of Computer Engineering and Science, Shanghai University, 99 Shang Da Road, Shanghai 200444, China.
Exp Neurol. 2018 Apr;302:214-229. doi: 10.1016/j.expneurol.2018.01.007. Epub 2018 Jan 12.
Astrocytes are known to regulate and support neuronal and synaptic functions. Changes in their size and morphology in mouse models result in mental retardation. However, the mechanism underlying these morphological changes remains unclear. In the present study, abnormal astrocyte morphology was found in the mouse brain following knockout of dendritic cell factor 1 (Dcf1). Immunoprecipitation-mass spectrometry (IP-Mass) identified that ATP1B1 is bound to DCF1, and co-immunoprecipitation and cell fluorescence further confirmed an interaction between these two proteins, with asparagine residue 266 of ATP1B1 being required for the interaction with DCF1. Moreover, Dcf1 knockout in mice resulted in upregulation of ATP1B1 expression in the hippocampus. Furthermore, DCF1 interaction with ATP1B1 in astrocytes impaired their structural plasticity. Ultimately, Dcf1 knockout increased glutamate release. Mechanism exploration proposed that Dcf1 knockout led to significantly perturbed expression of AMPA receptors (AMPARs) and induced morphological changes in astrocytes through the P38 signaling pathway. Our data shed light on the possible mechanisms underlying changes in astrocyte morphology and provide new avenues for the exploration of proteins involved in glutamate release.
星形胶质细胞被认为可以调节和支持神经元和突触功能。在小鼠模型中，它们的大小和形态的变化导致智力迟钝。然而，这些形态变化的机制尚不清楚。在本研究中，敲除树突细胞因子 1 (Dcf1) 后，在小鼠大脑中发现星形胶质细胞形态异常。免疫沉淀-质谱 (IP-Mass) 鉴定出 ATP1B1 与 DCF1 结合，共免疫沉淀和细胞荧光进一步证实了这两种蛋白质之间的相互作用，ATP1B1 的天冬酰胺残基 266 是与 DCF1 相互作用所必需的。此外，在小鼠中敲除 Dcf1 导致海马体中 ATP1B1 的表达上调。此外，星形胶质细胞中 DCF1 与 ATP1B1 的相互作用损害了它们的结构可塑性。最终，Dcf1 敲除增加了谷氨酸的释放。机制探索提出，Dcf1 敲除导致 AMPA 受体 (AMPAR) 的表达显著失调，并通过 P38 信号通路诱导星形胶质细胞形态变化。我们的数据为星形胶质细胞形态变化的可能机制提供了线索，并为探索参与谷氨酸释放的蛋白质提供了新的途径。
