Endophilin A1 drives acute structural plasticity of dendritic spines in response to Ca2+/calmodulin
Yanrui Yang, Chen Jiang, Xue Chen, Di Li, Jianfeng He, Shen Wang, Shun Zhao, Xiaoyu Yang, Shikun Deng, Chunfang Tong, Dou Wang, Zhenzhen Guo, Dong Li, Cong Ma, Xin Liang, Yun Stone Shi, Jia‐Jia Liu
Abstract
Induction of long-term potentiation (LTP) in excitatory neurons triggers a large transient increase in the volume of dendritic spines followed by decays to sustained size expansion, a process termed structural LTP (sLTP) that contributes to the cellular basis of learning and memory. Although mechanisms regulating the early and sustained phases of sLTP have been studied intensively, how the acute spine enlargement immediately after LTP stimulation is achieved remains elusive. Here, we report that endophilin A1 orchestrates membrane dynamics with actin polymerization to initiate spine enlargement in NMDAR-mediated LTP. Upon LTP induction, Ca2+/calmodulin enhances binding of endophilin A1 to both membrane and p140Cap, a cytoskeletal regulator. Consequently, endophilin A1 rapidly localizes to the plasma membrane and recruits p140Cap to promote local actin polymerization, leading to spine head expansion. Moreover, its molecular functions in activity-induced rapid spine growth are required for LTP and long-term memory. Thus, endophilin A1 serves as a calmodulin effector to drive acute structural plasticity necessary for learning and memory.