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bioRxiv · 10.1101/2021.02.09.430404

Synaptotagmin 7 is enriched at the plasma membrane to promote vesicle docking and control synaptic plasticity

Vevea, J. D.·Kusick, G. F.·Chen, E.·Courtney, K. C.·Watanabe, S.·Chapman, E. R.
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Abstract

Synaptotagmin (SYT) 7 has emerged as key regulator of presynaptic function, but its localization and precise function in the synaptic vesicle cycle remain unclear. Here, we used iGluSnFR to optically and directly interrogate glutamate release, at the single bouton level, in SYT7 KO dissociated mouse hippocampal neurons. We analyzed asynchronous release, paired pulse facilitation, and synaptic vesicle replenishment, and found that SYT7 contributes to each of these processes to different degrees. Zap-and-freeze electron microscopy revealed that loss of SYT7 impairs the docking of synaptic vesicles after a stimulus and the recovery of depleted synaptic vesicles after a stimulus train. To execute these functions, SYT7 must be targeted to the plasma membrane via {gamma}-secretase-mediated cleavage of the amino terminus, followed by palmitoylation. The complex sorting itinerary of SYT7 endows this Ca2+-sensor with the ability to control crucial forms of synaptic function and plasticity. O_LISYT7 mediated asynchronous release, paired pulse facilitation, and synaptic vesicle replenishment was observed optically at individual hippocampal synapses C_LIO_LILocalization, trafficking, and stability of SYT7 is dependent on processing by {gamma}-secretase C_LIO_LIShort term plasticity defects arise in SYT7KOs due to decreased docking of synaptic vesicles after stimulation C_LIO_LISYT7 promotes paired-pulse facilitation and asynchronous release via distinct mechanisms C_LI

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Vevea, J. D., Kusick, G. F., Chen, E., Courtney, K. C., Watanabe, S., Chapman, E. R.. 2021-02-09. Synaptotagmin 7 is enriched at the plasma membrane to promote vesicle docking and control synaptic plasticity. https://doi.org/10.1101/2021.02.09.430404

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