Yang Yanrui, Chen Jiang, Guo Zhenzhen, Deng Shikun, Du Xiangyang, Zhu Shaoxia, Ye Chang, Shi Yun S, Liu Jia-Jia
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.
Front Mol Neurosci. 2018 May 28;11:177. doi: 10.3389/fnmol.2018.00177. eCollection 2018.
Endophilin A1 is a member of the N-BAR domain-containing endophilin A protein family that is involved in membrane dynamics and trafficking. At the presynaptic terminal, endophilin As participate in synaptic vesicle recycling and autophagosome formation. By gene knockout studies, here we report that postsynaptic endophilin A1 functions in synaptic plasticity. Ablation of endophilin A1 in the hippocampal CA1 region of mature mouse brain impairs long-term spatial and contextual fear memory. Its loss in CA1 neurons postsynaptic of the Schaffer collateral pathway causes impairment in their AMPA-type glutamate receptor-mediated synaptic transmission and long-term potentiation. In KO neurons, defects in the structural and functional plasticity of dendritic spines can be rescued by overexpression of endophilin A1 but not A2 or A3. Further, endophilin A1 promotes actin polymerization in dendritic spines during synaptic potentiation. These findings reveal a physiological role of endophilin A1 distinct from that of other endophilin As at the postsynaptic site.
内吞蛋白A1是含N-BAR结构域的内吞蛋白A蛋白家族的成员，参与膜动力学和运输。在突触前末端，内吞蛋白A参与突触小泡循环和自噬体形成。通过基因敲除研究，我们在此报告突触后内吞蛋白A1在突触可塑性中发挥作用。在成熟小鼠大脑海马CA1区敲除内吞蛋白A1会损害长期空间和情境恐惧记忆。在沙氏侧支通路突触后的CA1神经元中缺失该蛋白会导致其AMPA型谷氨酸受体介导的突触传递和长时程增强受损。在基因敲除神经元中，树突棘结构和功能可塑性的缺陷可通过过表达内吞蛋白A1而非A2或A3来挽救。此外，内吞蛋白A1在突触增强过程中促进树突棘中的肌动蛋白聚合。这些发现揭示了内吞蛋白A1在突触后位点与其他内吞蛋白A不同的生理作用。
