Synaptotagmin‐11 inhibits spontaneous neurotransmission through vti1a
| Autor: | Wan-Ru Li, Feifan Zhang, Yalong Wang, Claire Xi Zhang, Chao Li, Jing-Chen Li, Meiqin Hu, Rena Li, Pei Gao, Shuli Zhang |
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| Rok vydání: | 2021 |
| Předmět: |
Gene isoform
Primary Cell Culture Central nervous system Neurotransmission Hippocampal formation Hippocampus Synaptic Transmission Biochemistry Synaptotagmin 1 Mice Synaptotagmins Cellular and Molecular Neuroscience medicine Animals Immunoprecipitation Gene Knock-In Techniques Mice Knockout Neurons Gene knockdown Chemistry Excitatory Postsynaptic Potentials Qb-SNARE Proteins Phenotype Electrophysiological Phenomena Cell biology Mice Inbred C57BL medicine.anatomical_structure Excitatory postsynaptic potential |
| Zdroj: | Journal of Neurochemistry. 159:729-741 |
| ISSN: | 1471-4159 0022-3042 |
| DOI: | 10.1111/jnc.15523 |
| Popis: | Recent work has revealed that spontaneous release plays critical roles in the central nervous system, but how it is regulated remains elusive. Here we report that synaptotagmin-11 (Syt11), a Ca2+ -independent Syt isoform associated with schizophrenia and Parkinson's disease, suppressed spontaneous release. Syt11-knockout hippocampal neurons showed an increased frequency of miniature excitatory postsynaptic currents while overexpression of Syt11 inversely decreased the frequency. Neither knockout nor overexpression of Syt11 affected the average amplitude, suggesting the presynaptic regulation of spontaneous neurotransmission by Syt11. Glutathione-S-transferase pull-down, co-immunoprecipitation, and affinity-purification experiments demonstrated a direct interaction of Syt11 with vps10p-tail-interactor-1a (vti1a), a non-canonical SNARE protein that maintains spontaneous release. Importantly, knockdown of vti1a reversed the phenotype of Syt11 knockout, identifying vti1a as the main target of Syt11 inhibition. Domain analysis revealed that the C2A domain of Syt11 bound vti1a with high affinity. Consistently, expression of the C2A domain alone rescued the phenotype of elevated spontaneous release in Syt11-knockout neurons similar to the full-length protein. Altogether, our results suggest that Syt11 inhibits vti1a-containing vesicles during spontaneous release. |
| Databáze: | OpenAIRE |
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