Munc13 supports fusogenicity of non-docked vesicles at synapses with disrupted active zones
2022 | journal article. A publication with affiliation to the University of Göttingen.
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- Authors
- Tan, Chao; de Nola, Giovanni; Qiao, Claire; Imig, Cordelia; Born, Richard T.; Brose, Nils ; Kaeser, Pascal S.
- 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 Ca 2+ 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.
- Issue Date
- 2022
- Journal
- eLife
- Project
- EXC 2067: Multiscale Bioimaging
- Working Group
- RG Brose
- eISSN
- 2050-084X
- Language
- English
- Sponsor
- National Institute of Mental Health http://dx.doi.org/10.13039/100000025
National Institute of Neurological Disorders and Stroke http://dx.doi.org/10.13039/100000065
Harvard Medical School http://dx.doi.org/10.13039/100006691
Max Planck Institute for Multidisciplinary Sciences
German Research Foundation http://dx.doi.org/10.13039/501100001659