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

Cell Research
Yanrui YangJia-Jia Liu

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.

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Citations

Mar 13, 2016·Cellular and Molecular Life Sciences : CMLS·Dieudonnée van de WilligeAnna Akhmanova
Dec 29, 2016·Proceedings of the National Academy of Sciences of the United States of America·Chunyi LiuShilai Bao
Jul 7, 2017·Clinical and Experimental Hypertension : CHE·Hongmei LiXiaojie Zhang
Jun 4, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Bethany J SanstrumNicholas G James
Jul 13, 2018·Frontiers in Neuroscience·Peter VerstraelenWinnok H De Vos
Dec 24, 2018·International Journal of Molecular Sciences·Xiao Wen MaoMichael J Pecaut
Jun 13, 2018·Frontiers in Molecular Neuroscience·Yanrui YangJia-Jia Liu
Mar 14, 2021·Nature Nanotechnology·Joshua J RennickRobert G Parton

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