Synapse and Active Zone Assembly in the Absence of Presynaptic Ca²⁺ Channels and Ca²⁺ Entry, Neuron, 19 Aug 2020

Neuron, 19 August, 2020, DOI：https://doi.org/10.1016/j.neuron.2020.05.032

Synapse and Active Zone Assembly in the Absence of Presynaptic Ca²⁺ Channels and Ca²⁺ Entry

Richard G.Held, Changliang Liu, Kunpeng Ma, Austin M.Ramsey, Tyler B.Tarr, Giovanni De Nola, Shan Shan H.Wang, Jiexin Wang, Arn M.J.M.van den Maagdenberg, Toni Schneider, Jianyuan Sun, Thomas A.Blanpied, Pascal S.Kaeser

Summary

Presynaptic Ca_V2 channels are essential for Ca²⁺-triggered exocytosis. In addition, there are two competing models for their roles in synapse structure. First, Ca²⁺ channels or Ca²⁺ entry may control synapse assembly. Second, active zone proteins may scaffold Ca_V2s to presynaptic release sites, and synapse structure is Ca_V2 independent. Here, we ablated all three Ca_V2s using conditional knockout in cultured hippocampal neurons or at the calyx of Held, which abolished evoked exocytosis. Compellingly, synapse and active zone structure, vesicle docking, and transsynaptic nano-organization were unimpaired. Similarly, long-term blockade of action potentials and Ca²⁺ entry did not disrupt active zone assembly. Although Ca_V2 knockout impaired the localization of β subunits, α2δ-1 localized normally. Rescue with Ca_V2 restored exocytosis, and Ca_V2 active zone targeting depended on the intracellular C-terminus. We conclude that synapse assembly is independent of Ca_V2s or Ca²⁺ entry through them. Instead, active zone proteins recruit and anchor Ca_V2s via Ca_V2 C-termini.

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