Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Held, Richard G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Liu, Changliang UNSPECIFIED orcid.org/0000-0002-0915-8408 UNSPECIFIED Ma, Kunpeng UNSPECIFIED UNSPECIFIED UNSPECIFIED Ramsey, Austin M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Tarr, Tyler B. UNSPECIFIED UNSPECIFIED UNSPECIFIED De Nola, Giovanni UNSPECIFIED UNSPECIFIED UNSPECIFIED Wang, Shan Shan H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wang, Jiexin UNSPECIFIED UNSPECIFIED UNSPECIFIED van den Maagdenberg, Arn M. J. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schneider, Toni UNSPECIFIED UNSPECIFIED UNSPECIFIED Sun, Jianyuan UNSPECIFIED UNSPECIFIED UNSPECIFIED Blanpied, Thomas A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kaeser, Pascal S. UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language CALCIUM-CHANNELS; BETA-SUBUNIT; NEUROTRANSMITTER RELEASE; TRANSMITTER RELEASE; CA(V)1.3 CHANNELS; VESICLE DOCKING; PROTEIN; BINDING; CELLS; SITE Multiple languages Neurosciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/32296