Munc13 supports fusogenicity of non-docked vesicles at synapses with disrupted active zones
Research output: Contribution to journal › Journal article › Research › peer-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 journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
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