Munc13 supports fusogenicity of non-docked vesicles at synapses with disrupted active zones

Research output: Contribution to journalJournal articlepeer-review

Standard

Munc13 supports fusogenicity of non-docked vesicles at synapses with disrupted active zones. / Tan, Chao; Nola, Giovanni de; Qiao, Claire; Imig, Cordelia; Born, Richard T; Brose, Nils; Kaeser, Pascal S.

In: eLife, Vol. 11, :e79077, 2022.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Tan, C, Nola, GD, Qiao, C, Imig, C, Born, RT, Brose, N & Kaeser, PS 2022, 'Munc13 supports fusogenicity of non-docked vesicles at synapses with disrupted active zones', eLife, vol. 11, :e79077. https://doi.org/10.7554/eLife.79077

APA

Tan, C., Nola, G. D., Qiao, C., Imig, C., Born, R. T., Brose, N., & Kaeser, P. S. (2022). Munc13 supports fusogenicity of non-docked vesicles at synapses with disrupted active zones. eLife, 11, [:e79077]. https://doi.org/10.7554/eLife.79077

Vancouver

Tan C, Nola GD, Qiao C, Imig C, Born RT, Brose N et al. Munc13 supports fusogenicity of non-docked vesicles at synapses with disrupted active zones. eLife. 2022;11. :e79077. https://doi.org/10.7554/eLife.79077

Author

Tan, Chao ; Nola, Giovanni de ; Qiao, Claire ; Imig, Cordelia ; Born, Richard T ; Brose, Nils ; Kaeser, Pascal S. / Munc13 supports fusogenicity of non-docked vesicles at synapses with disrupted active zones. In: eLife. 2022 ; Vol. 11.

Bibtex

@article{cd84bf9796274d6f9f761a661c3b45f4,
title = "Munc13 supports fusogenicity of non-docked vesicles at synapses with disrupted active zones",
abstract = "Active zones consist of protein scaffolds that are tightly attached to the presynaptic plasma membrane. They dock and prime synaptic vesicles, couple them to voltage-gated Ca2+ channels, and direct neurotransmitter release towards postsynaptic receptor domains. Simultaneous RIM+ELKS ablation disrupts these scaffolds, abolishes vesicle docking and removes active zone-targeted Munc13, but some vesicles remain releasable. To assess whether this enduring vesicular fusogenicity is mediated by non-active zone-anchored Munc13 or is Munc13-independent, we ablated Munc13-1 and Munc13-2 in addition to RIM+ELKS in mouse hippocampal neurons. The hextuple knockout synapses lacked docked vesicles, but other ultrastructural features were near-normal despite the strong genetic manipulation. Removing Munc13 in addition to RIM+ELKS impaired action potential-evoked vesicle fusion more strongly than RIM+ELKS knockout by further decreasing the releasable vesicle pool. Hence, Munc13 can support some fusogenicity without RIM and ELKS, and presynaptic recruitment of Munc13, even without active zone-anchoring, suffices to generate some fusion-competent vesicles",
author = "Chao Tan and Nola, {Giovanni de} and Claire Qiao and Cordelia Imig and Born, {Richard T} and Nils Brose and Kaeser, {Pascal S}",
year = "2022",
doi = "10.7554/eLife.79077",
language = "English",
volume = "11",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications Ltd.",

}

RIS

TY - JOUR

T1 - Munc13 supports fusogenicity of non-docked vesicles at synapses with disrupted active zones

AU - Tan, Chao

AU - Nola, Giovanni de

AU - Qiao, Claire

AU - Imig, Cordelia

AU - Born, Richard T

AU - Brose, Nils

AU - Kaeser, Pascal S

PY - 2022

Y1 - 2022

N2 - Active zones consist of protein scaffolds that are tightly attached to the presynaptic plasma membrane. They dock and prime synaptic vesicles, couple them to voltage-gated Ca2+ channels, and direct neurotransmitter release towards postsynaptic receptor domains. Simultaneous RIM+ELKS ablation disrupts these scaffolds, abolishes vesicle docking and removes active zone-targeted Munc13, but some vesicles remain releasable. To assess whether this enduring vesicular fusogenicity is mediated by non-active zone-anchored Munc13 or is Munc13-independent, we ablated Munc13-1 and Munc13-2 in addition to RIM+ELKS in mouse hippocampal neurons. The hextuple knockout synapses lacked docked vesicles, but other ultrastructural features were near-normal despite the strong genetic manipulation. Removing Munc13 in addition to RIM+ELKS impaired action potential-evoked vesicle fusion more strongly than RIM+ELKS knockout by further decreasing the releasable vesicle pool. Hence, Munc13 can support some fusogenicity without RIM and ELKS, and presynaptic recruitment of Munc13, even without active zone-anchoring, suffices to generate some fusion-competent vesicles

AB - Active zones consist of protein scaffolds that are tightly attached to the presynaptic plasma membrane. They dock and prime synaptic vesicles, couple them to voltage-gated Ca2+ channels, and direct neurotransmitter release towards postsynaptic receptor domains. Simultaneous RIM+ELKS ablation disrupts these scaffolds, abolishes vesicle docking and removes active zone-targeted Munc13, but some vesicles remain releasable. To assess whether this enduring vesicular fusogenicity is mediated by non-active zone-anchored Munc13 or is Munc13-independent, we ablated Munc13-1 and Munc13-2 in addition to RIM+ELKS in mouse hippocampal neurons. The hextuple knockout synapses lacked docked vesicles, but other ultrastructural features were near-normal despite the strong genetic manipulation. Removing Munc13 in addition to RIM+ELKS impaired action potential-evoked vesicle fusion more strongly than RIM+ELKS knockout by further decreasing the releasable vesicle pool. Hence, Munc13 can support some fusogenicity without RIM and ELKS, and presynaptic recruitment of Munc13, even without active zone-anchoring, suffices to generate some fusion-competent vesicles

U2 - 10.7554/eLife.79077

DO - 10.7554/eLife.79077

M3 - Journal article

C2 - 36398873

VL - 11

JO - eLife

JF - eLife

SN - 2050-084X

M1 - :e79077

ER -

ID: 328300118