Endophilin A1 Promotes Actin Polymerization in Dendritic Spines Required for Synaptic Potentiation

Yanrui Yang; Jiang Chen; Zhenzhen Guo; Shikun Deng; Xiangyang Du; Shaoxia Zhu; Chang Ye; Yun S Shi; Jia-Jia Liu

doi:10.3389/fnmol.2018.00177

Endophilin A1 Promotes Actin Polymerization in Dendritic Spines Required for Synaptic Potentiation

Front Mol Neurosci. 2018 May 28:11:177. doi: 10.3389/fnmol.2018.00177. eCollection 2018.

Authors

Yanrui Yang^{1

2}, Jiang Chen³, Zhenzhen Guo^{1

2

4}, Shikun Deng^{1

2

4}, Xiangyang Du^{1

4}, Shaoxia Zhu^{1

2}, Chang Ye³, Yun S Shi³, Jia-Jia Liu^{1

2

5}

Affiliations

¹ State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
² CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.
³ State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, China.
⁴ Graduate School, University of Chinese Academy of Sciences, Beijing, China.
⁵ College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.

Abstract

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.

Keywords: AMPAR; actin polymerization; dendritic spine; endophilin A1; learning and memory; structural plasticity; synaptic potentiation; synaptic transmission.