摘要
目的研究α-突触核蛋白(α-synuclein,α-Syn)对N-甲基-D-天冬氨酸(N-methyl-D-aspartic acid receptors,NMDA)受体的调控及机制。方法在原代海马神经元,通过细胞外添加基因重组α-Syn和基因过表达α-Syn方法实现细胞内α-Syn含量增高,基因敲减技术抑制Rab5B,Western blotting法分析NMDA受体NR1亚单位和Rab5B表达。结果神经元内α-Syn含量增高可以使Rab5B表达上调,并降低膜表面NR1的水平;抑制Rab5B表达可有效反转α-Syn所致的膜表面NR1水平下降。结论α-Syn通过上调Rab5B促进NMDA受体的内在化。
Objective To investigate the effect of α-synuclein（α-Syn） on surface N-methyl-D-aspartic acid receptors（NMDARs） in cultured rat hippocampal neurons.Methods Increased intracellular α-Syn was realized by extracellular addition of recombinant human α-Syn to the culture medium or transfection of human α-Syn gene to the neurons.Western blotting analysis was applied to observe the effects of α-Syn on levels of NMDA receptor NR1 subunit and Rab5B under conditions with or without Rab5B knockdown.Results Intracellular elevation of α-Syn decreased the surface expression of NMDA NR1 and cytoplasmic levels of Rab5B;Inhibition of Rab5B expression reversed the effects of α-Syn.Conclusion The accumulation of α-Syn in hippocampal neurons can promote the internalization of surface NMDARs through an endocytic mechanism that requires participation of Rab5B.
出处
《首都医科大学学报》
CAS
北大核心
2017年第6期863-867,共5页
Journal of Capital Medical University
基金
国家自然科学基金(81371200
81071014
81401042)
北京市医院管理局"使命"计划专项经费资助(SML20150803)
北京市科学技术委员会资助(Z161100005116011
Z171100000117013)
北京市卫生和计划生育委员会项目(PXM2017_026283_000002)
广西自然科学基金(2014GXNSFAA118197)~~
