Volume 25, No 4, Apr 2015
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 25 Issue 4, April 2015: 496-516
ORIGINAL ARTICLES
Endophilin A1 regulates dendritic spine morphogenesis and stability through interaction with p140Cap
Yanrui Yang1,2, Mengping Wei3,4, Ying Xiong5, Xiangyang Du1,2,6, Shaoxia Zhu1,2, Lin Yang1, Chen Zhang3,4 and Jia-Jia Liu1,2
1State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Beijing 100101, China
2CAS Center for Excellence in Brain Science, Chinese Academy of Sciences, Beijing 100101, China
3State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Beijing 100871, China
4PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China
5School of Life Sciences, University of Science and Technology of China, Hefei Anhui 230026, China
6University of Chinese Academy of Sciences, Beijing 100039, China
Correspondence: Jia-Jia Liu(jjliu@genetics.ac.cn)
Dendritic spines are actin-rich membrane protrusions that are the major sites of excitatory synaptic input in the mammalian brain, and their morphological plasticity provides structural basis for learning and memory. Here we report that endophilin A1, with a well-established role in clathrin-mediated synaptic vesicle endocytosis at the presynaptic terminal, also localizes to dendritic spines and is required for spine morphogenesis, synapse formation and synaptic function. We identify p140Cap, a regulator of cytoskeleton reorganization, as a downstream effector of endophilin A1 and demonstrate that disruption of their interaction impairs spine formation and maturation. Moreover, we demonstrate that knockdown of endophilin A1 or p140Cap impairs spine stabilization and synaptic function. We further show that endophilin A1 regulates the distribution of p140Cap and its downstream effector, the F-actin-binding protein cortactin as well as F-actin enrichment in dendritic spines. Together, these results reveal a novel function of postsynaptic endophilin A1 in spine morphogenesis, stabilization and synaptic function through the regulation of p140Cap.
10.1038/cr.2015.31
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