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bioRxiv · 10.1101/2020.05.07.082081

Endophilin A1 promotes Actin Polymerization in response to Ca2+/calmodulin to Initiate Structural Plasticity of Dendritic Spines

Liu, J.-J.·Yang, Y.·Chen, J.·Chen, X.·Li, D.·He, J.·Zhao, S.·Yang, X.·Deng, S.·Wang, D.·Guo, Z.·Zhu, S.·Ma, C.·Liang, X.·Shi, Y. S.
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Abstract

Dendritic spines of excitatory neurons undergo activity-dependent structural and functional plasticity, which are cellular correlates of learning and memory. However, mechanisms underlying the rapid morphological changes immediately after NMDAR-mediated Ca2+ influx into spines remain poorly understood. Here we report that endophilin A1, a neuronal N-BAR protein, orchestrates membrane dynamics with actin polymerization to initiate spine enlargement in the induction phase of long-term potentiation (LTP). Upon LTP induction, Ca2+/calmodulin enhances its binding to both membrane and p140Cap, a cytoskeleton regulator. As a result, endophilin A1 rapidly associates with the relaxed plasma membrane and promotes actin polymerization, leading to acute expansion of spine head. Moreover, not only the p140Cap-binding, but also calmodulin- and membrane-binding capacities of endophilin A1 are required for LTP and long-term memory. Thus, endophilin A1 functions as calmodulin effector to drive spine enlargement in response to Ca2+ influx in the initial phase of structural plasticity.

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Liu, J.-J., Yang, Y., Chen, J., Chen, X., Li, D., He, J., Zhao, S., Yang, X., Deng, S., Wang, D., Guo, Z., Zhu, S., Ma, C., Liang, X., Shi, Y. S.. 2020-05-08. Endophilin A1 promotes Actin Polymerization in response to Ca2+/calmodulin to Initiate Structural Plasticity of Dendritic Spines. https://doi.org/10.1101/2020.05.07.082081

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