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

机译:突触和有源区组装在没有预先突触式CA2 +通道和CA2 +条目的情况下

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摘要

Presynaptic Ca(v)2 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(v)2s to presynaptic release sites, and synapse structure is Ca(v)2 independent. Here, we ablated all three Ca(v)2s 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(v)2 knockout impaired the localization of beta subunits, alpha 2 delta-1 localized normally. Rescue with Ca(v)2 restored exocytosis, and Ca(v)2 active zone targeting depended on the intracellular C-terminus. We conclude that synapse assembly is independent of Ca(v)2s or Ca2+ entry through them. Instead, active zone proteins recruit and anchor Ca(v)2s via Ca(v)2 C-termini.
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  • 来源
    《Neuron》 |2020年第4期|共26页
  • 作者单位

    Harvard Med Sch Dept Neurobiol Boston MA 02115 USA;

    Harvard Med Sch Dept Neurobiol Boston MA 02115 USA;

    Harvard Med Sch Dept Neurobiol Boston MA 02115 USA;

    Univ Maryland Dept Physiol &

    Program Neurosci Sch Med Baltimore MD 21201 USA;

    Univ Maryland Dept Physiol &

    Program Neurosci Sch Med Baltimore MD 21201 USA;

    Harvard Med Sch Dept Neurobiol Boston MA 02115 USA;

    Harvard Med Sch Dept Neurobiol Boston MA 02115 USA;

    Harvard Med Sch Dept Neurobiol Boston MA 02115 USA;

    Leiden Univ Dept Human Genet Med Ctr NL-2333 ZA Leiden Netherlands;

    Univ Cologne Inst Neurophysiol D-50931 Cologne Germany;

    Chinese Acad Sci Inst Biophys State Key Lab Brain &

    Cognit Sci Beijing 100101 Peoples R China;

    Univ Maryland Dept Physiol &

    Program Neurosci Sch Med Baltimore MD 21201 USA;

    Harvard Med Sch Dept Neurobiol Boston MA 02115 USA;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 神经病学;
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