title: Endophilin A1 regulates dendritic spine morphogenesis and stability through interaction with p140Cap.
abstract: 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.
authors.affiliation: 1] State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Beijing 100101, China [2] CAS Center for Excellence in Brain Science, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yanrui
authors.initials: Y
authors.lastname: Yang
authors.affiliation: 1] State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Beijing 100871, China [2] PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.
authors.forename: Mengping
authors.initials: M
authors.lastname: Wei
authors.affiliation: School of Life Sciences, University of Science and Technology of China, Hefei Anhui 230026, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: 1] State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Beijing 100101, China [2] CAS Center for Excellence in Brain Science, Chinese Academy of Sciences, Beijing 100101, China [3] University of Chinese Academy of Sciences, Beijing 100039, China.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Du
authors.affiliation: 1] State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Beijing 100101, China [2] CAS Center for Excellence in Brain Science, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Shaoxia
authors.initials: S
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Beijing 100101, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.affiliation: 1] State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Beijing 100871, China [2] PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.affiliation: 1] State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Beijing 100101, China [2] CAS Center for Excellence in Brain Science, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jia-Jia
authors.initials: JJ
authors.lastname: Liu
mesh_terms: D008841:Actin Cytoskeleton / Q000235:genetics; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D049229:Dendritic Spines / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D009024:Morphogenesis / Q000235:genetics*; D055495:Neurogenesis / Q000235:genetics; D009473:Neuronal Plasticity / Q000235:genetics; D009474:Neurons / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; C532615:SRCIN1 protein, human; C504641:endophilin A1 protein, mouse