Synaptotagmin 7 docks synaptic vesicles for Doc2α-triggered asynchronous neurotransmitter release
Publikation: Working paper › Preprint › Forskning
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Synaptotagmin 7 docks synaptic vesicles for Doc2α-triggered asynchronous neurotransmitter release. / Wu, Zhenyong; Kusick, Grant; Berns, Manon; Raychaudhuri, Sumana; Itoh, Kie; Walter, Alexander; Chapman, Edwin; Watanabe, Shigeki.
2022.Publikation: Working paper › Preprint › Forskning
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T1 - Synaptotagmin 7 docks synaptic vesicles for Doc2α-triggered asynchronous neurotransmitter release
AU - Wu, Zhenyong
AU - Kusick, Grant
AU - Berns, Manon
AU - Raychaudhuri, Sumana
AU - Itoh, Kie
AU - Walter, Alexander
AU - Chapman, Edwin
AU - Watanabe, Shigeki
PY - 2022
Y1 - 2022
N2 - The molecular basis of asynchronous neurotransmitter release remains enigmatic despite decades of intense study. Synaptotagmin (syt) 7 and Doc2 have both been proposed as Ca2+ sensors that trigger this mode of exocytosis, but conflicting findings have led to controversy. Here, we demonstrate that at excitatory mouse hippocampal synapses from cultured neurons and acute slices, Doc2α is the major Ca2+ sensor for asynchronous release, while syt7 supports this process through activity-dependent docking of synaptic vesicles. In synapses lacking Doc2α, asynchronous release after single action potentials is strongly reduced, while deleting syt7 has no effect. However, in the absence of syt7, docked vesicles cannot recover on millisecond timescales. Consequently, both synchronous and asynchronous release depress from the second pulse on during repetitive activity. By contrast, synapses lacking Doc2α have normal activity-dependent docking, but continue to exhibit decreased asynchronous release after multiple stimuli. Moreover, disruption of both Ca2+ sensors is non-additive. These findings result in a new model whereby syt7 drives activity-dependent docking, thus ‘feeding’ synaptic vesicles to Doc2 for asynchronous release during ongoing transmission
AB - The molecular basis of asynchronous neurotransmitter release remains enigmatic despite decades of intense study. Synaptotagmin (syt) 7 and Doc2 have both been proposed as Ca2+ sensors that trigger this mode of exocytosis, but conflicting findings have led to controversy. Here, we demonstrate that at excitatory mouse hippocampal synapses from cultured neurons and acute slices, Doc2α is the major Ca2+ sensor for asynchronous release, while syt7 supports this process through activity-dependent docking of synaptic vesicles. In synapses lacking Doc2α, asynchronous release after single action potentials is strongly reduced, while deleting syt7 has no effect. However, in the absence of syt7, docked vesicles cannot recover on millisecond timescales. Consequently, both synchronous and asynchronous release depress from the second pulse on during repetitive activity. By contrast, synapses lacking Doc2α have normal activity-dependent docking, but continue to exhibit decreased asynchronous release after multiple stimuli. Moreover, disruption of both Ca2+ sensors is non-additive. These findings result in a new model whereby syt7 drives activity-dependent docking, thus ‘feeding’ synaptic vesicles to Doc2 for asynchronous release during ongoing transmission
U2 - 10.1101/2022.04.21.489101
DO - 10.1101/2022.04.21.489101
M3 - Preprint
BT - Synaptotagmin 7 docks synaptic vesicles for Doc2α-triggered asynchronous neurotransmitter release
ER -
ID: 334078933