Endophilin A1 regulates dendritic spine morphogenesis and stability through interaction with p140Cap  

作　　者：Yanrui Yang Mengping Wei Ying Xiong Xiangyang Du Shaoxia Zhu Lin Yang Chen Zhang Jia-Jia Liu 

机构地区：[1]State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology [2]CAS Center for Excellence in Brain Science, Chinese Academy of Sciences, Beijing 100101, China [3]State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences [4]PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China [5]School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China [6]University of Chinese Academy of Sciences, Beij'ing 100039, China

出　　处：《Cell Research》2015年第4期496-516,共21页细胞研究（英文版）

基　　金：We are indebted to our colleagues for providing reagents （Dr Xinyu Zhao, University of Wisconsin, Madison, USA; Dr Casper C Hoogenraad, Utrecht University, The Netherlands and Dr Evelyne Coudrier, Institut Curie, France） and for critical comments on the manuscript （Dr Tieshan Tang, Institute of Zoology, Chinese Academy of Sciences, China）. We are grateful to Dr Lan Bao （Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, China）, Dr Hongli Feng, Dr Ping Zhu and Lei Sun （Institute of Biophysics, Chinese Academy of Sciences, China） for technical assistance and advices on electron microscopy. This work was supported by the National Basic Research Program （2014CB942802 to J-JL and CZ, 2011CB965002 to J-JL）, the Na- tional Natural Science Foundation of China （31325017, 30830059 to J-JL, 31222025, 31171025 to CZ） and CAS Key Project （KSCX2-EW-R-05 to J-JL）. YY was supported by Young Scientist Award from the National Natural Science Foundation of China （30900718）.

摘　　要：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 pre- synaptic terminal, also localizes to dendritic spines and is required for spine morphogenesis, synapse formation and synaptic function. We identify pl40Cap, a regulator of cytoskeleton reorganization, as a downstream effector of en- dophilin A1 and demonstrate that disruption of their interaction impairs spine formation and maturation. Moreover, we demonstrate that knockdown of endophUin A1 or pl40Cap impairs spine stabilization and synaptic function. We further show that endophilin A1 regulates the distribution of pl40Cap 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 pl40Cap.

关 键 词：endophilin A1 p 140Cap spine morphogenesis actin cytoskeleton synapse formation 

分 类 号：Q948.1[生物学—植物学] S831.1[农业科学—畜牧学]