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

التفاصيل البيبلوغرافية
العنوان: Munc13 supports fusogenicity of non-docked vesicles at synapses with disrupted active zones
المؤلفون: Chao Tan, Giovanni de Nola, Claire Qiao, Cordelia Imig, Richard T Born, Nils Brose, Pascal S Kaeser
المصدر: eLife, Vol 11 (2022)
بيانات النشر: eLife Sciences Publications Ltd, 2022.
سنة النشر: 2022
المجموعة: LCC:Medicine
LCC:Science
LCC:Biology (General)
مصطلحات موضوعية: synapse, active zone, munc13, readily releasable pool, synaptic vesicle priming, fusion competence, Medicine, Science, Biology (General), QH301-705.5
الوصف: 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 toward 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.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2050-084X
Relation: https://elifesciences.org/articles/79077; https://doaj.org/toc/2050-084X
DOI: 10.7554/eLife.79077
URL الوصول: https://doaj.org/article/6ec176feae324d379848db5a0ace7351
رقم الأكسشن: edsdoj.6ec176feae324d379848db5a0ace7351
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:2050084X
DOI:10.7554/eLife.79077