| First Author | Held RG | Year | 2020 |
| Journal | Neuron | Volume | 107 |
| Issue | 4 | Pages | 667-683.e9 |
| PubMed ID | 32616470 | Mgi Jnum | J:294995 |
| Mgi Id | MGI:6458169 | Doi | 10.1016/j.neuron.2020.05.032 |
| Citation | Held RG, et al. (2020) Synapse and Active Zone Assembly in the Absence of Presynaptic Ca(2+) Channels and Ca(2+) Entry. Neuron 107(4):667-683.e9 |
| abstractText | Presynaptic CaV2 channels are essential for Ca(2+)-triggered exocytosis. In addition, there are two competing models for their roles in synapse structure. First, Ca(2+) channels or Ca(2+) entry may control synapse assembly. Second, active zone proteins may scaffold CaV2s to presynaptic release sites, and synapse structure is CaV2 independent. Here, we ablated all three CaV2s 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 Ca(2+) entry did not disrupt active zone assembly. Although CaV2 knockout impaired the localization of beta subunits, alpha2delta-1 localized normally. Rescue with CaV2 restored exocytosis, and CaV2 active zone targeting depended on the intracellular C-terminus. We conclude that synapse assembly is independent of CaV2s or Ca(2+) entry through them. Instead, active zone proteins recruit and anchor CaV2s via CaV2 C-termini. |
