Synapse and Active Zone Assembly in the Absence of Presynaptic Ca 2+ Channels and Ca 2+ Entry.

Autor: Held RG; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA., Liu C; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA., Ma K; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA; State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, and University of Chinese Academy of Sciences, Beijing 100101, China., Ramsey AM; Department of Physiology and Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD 21201, USA., Tarr TB; Department of Physiology and Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD 21201, USA., De Nola G; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA., Wang SSH; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA., Wang J; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA., van den Maagdenberg AMJM; Departments of Human Genetics and Neurology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands., Schneider T; Institute for Neurophysiology, University of Cologne, Köln 50931, Germany., Sun J; State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, and University of Chinese Academy of Sciences, Beijing 100101, China., Blanpied TA; Department of Physiology and Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD 21201, USA., Kaeser PS; Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: kaeser@hms.harvard.edu.
Jazyk: angličtina
Zdroj: Neuron [Neuron] 2020 Aug 19; Vol. 107 (4), pp. 667-683.e9. Date of Electronic Publication: 2020 Jun 16.
DOI: 10.1016/j.neuron.2020.05.032
Abstrakt: Presynaptic Ca V 2 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 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 Ca 2+ entry did not disrupt active zone assembly. Although Ca V 2 knockout impaired the localization of β subunits, α2δ-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 Ca 2+ entry through them. Instead, active zone proteins recruit and anchor Ca V 2s via Ca V 2 C-termini.
Competing Interests: Declaration of Interests The authors declare no competing interests. S.S.H.W. is currently an employee of RA Capital Management, LP.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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