Held, Richard G., Liu, Changliang ORCID: 0000-0002-0915-8408, Ma, Kunpeng, Ramsey, Austin M., Tarr, Tyler B., De Nola, Giovanni, Wang, Shan Shan H., Wang, Jiexin, van den Maagdenberg, Arn M. J. M., Schneider, Toni, Sun, Jianyuan, Blanpied, Thomas A. and Kaeser, Pascal S. (2020). Synapse and Active Zone Assembly in the Absence of Presynaptic Ca2+ Channels and Ca2+ Entry. Neuron, 107 (4). S. 667 - 693. CAMBRIDGE: CELL PRESS. ISSN 1097-4199

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Abstract

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Held, Richard G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liu, ChangliangUNSPECIFIEDorcid.org/0000-0002-0915-8408UNSPECIFIED
Ma, KunpengUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ramsey, Austin M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tarr, Tyler B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
De Nola, GiovanniUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wang, Shan Shan H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wang, JiexinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van den Maagdenberg, Arn M. J. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schneider, ToniUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sun, JianyuanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blanpied, Thomas A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kaeser, Pascal S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-322962
DOI: 10.1016/j.neuron.2020.05.032
Journal or Publication Title: Neuron
Volume: 107
Number: 4
Page Range: S. 667 - 693
Date: 2020
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1097-4199
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CALCIUM-CHANNELS; BETA-SUBUNIT; NEUROTRANSMITTER RELEASE; TRANSMITTER RELEASE; CA(V)1.3 CHANNELS; VESICLE DOCKING; PROTEIN; BINDING; CELLS; SITEMultiple languages
NeurosciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/32296

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