Fast resupply of synaptic vesicles requires synaptotagmin-3.

Autor: Weingarten DJ; Vollum Institute, Oregon Health and Science University, Portland, OR, USA., Shrestha A; Vollum Institute, Oregon Health and Science University, Portland, OR, USA., Juda-Nelson K; Vollum Institute, Oregon Health and Science University, Portland, OR, USA., Kissiwaa SA; Vollum Institute, Oregon Health and Science University, Portland, OR, USA., Spruston E; Vollum Institute, Oregon Health and Science University, Portland, OR, USA., Jackman SL; Vollum Institute, Oregon Health and Science University, Portland, OR, USA. jackmans@ohsu.edu.
Jazyk: angličtina
Zdroj: Nature [Nature] 2022 Nov; Vol. 611 (7935), pp. 320-325. Date of Electronic Publication: 2022 Oct 19.
DOI: 10.1038/s41586-022-05337-1
Abstrakt: Sustained neuronal activity demands a rapid resupply of synaptic vesicles to maintain reliable synaptic transmission. Such vesicle replenishment is accelerated by submicromolar presynaptic Ca 2+ signals by an as-yet unidentified high-affinity Ca 2+ sensor 1,2 . Here we identify synaptotagmin-3 (SYT3) 3,4 as that presynaptic high-affinity Ca 2+ sensor, which drives vesicle replenishment and short-term synaptic plasticity. Synapses in Syt3 knockout mice exhibited enhanced short-term depression, and recovery from depression was slower and insensitive to presynaptic residual Ca 2+ . During sustained neuronal firing, SYT3 accelerated vesicle replenishment and increased the size of the readily releasable pool. SYT3 also mediated short-term facilitation under conditions of low release probability and promoted synaptic enhancement together with another high-affinity synaptotagmin, SYT7 (ref. 5 ). Biophysical modelling predicted that SYT3 mediates both replenishment and facilitation by promoting the transition of loosely docked vesicles to tightly docked, primed states. Our results reveal a crucial role for presynaptic SYT3 in the maintenance of reliable high-frequency synaptic transmission. Moreover, multiple forms of short-term plasticity may converge on a mechanism of reversible, Ca 2+ -dependent vesicle docking.
(© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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