Endophilin A1 regulates dendritic spine morphogenesis and stability through interaction with p140Cap
Endophilin A1 regulates dendritic spine morphogenesis and stability through interaction with p140Cap
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DOI：
10.1038/cr.2015.31
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发表时间：
2015-03
期刊：
影响因子：
44.1
通讯作者：
Yanrui Yang;Mengping Wei;Ying Xiong;Xiangyang Du;Shaoxia Zhu;Lin Yang;Chen Zhang;Jia-Jia Liu-Jia
中科院分区：
文献类型：
--
作者：
Yanrui Yang;Mengping Wei;Ying Xiong;Xiangyang Du;Shaoxia Zhu;Lin Yang;Chen Zhang;Jia-Jia Liu-Jia
树突棘是富含肌动蛋白的膜突起，是哺乳动物大脑兴奋性突触输入的主要部位，其形态的可塑性为学习记忆提供了结构基础。在这里，我们报道了在突触前末端的网格蛋白介导的突触囊泡内吞作用中具有明确作用的嗜内蛋白A1，也定位于树突棘，并且是脊柱形态发生、突触形成和突触功能所必需的。我们发现细胞骨架重组的调节因子p140Cap是亲内肽A1的下游效应因子，并证明破坏它们的相互作用会损害脊柱的形成和成熟。此外，我们证明了内啡肽A1或p140Cap的下调会损害脊柱稳定和突触功能。我们进一步发现，亲内蛋白A1调节p140Cap及其下游效应物、f -肌动蛋白结合蛋白的分布以及f -肌动蛋白在树突棘中的富集。总之，这些结果揭示了突触后嗜内肽A1通过调节p140Cap在脊柱形态发生、稳定和突触功能中的新功能。
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.