Synaptotagmin-1 serves as a primary Zn²⁺ sensor to mediate spontaneous neurotransmitter release under pathological conditions.

ABSTRACT: In the pre-synapse, vesicle fusion is a crucial process for neurotransmitter release in the nervous system. Under physiological conditions, synaptotagmin-1 (Syt1) locks synaptic vesicles in a priming state, allowing them to undergo synchronized neurotransmitter release upon Ca²⁺ activation. Elevation of intracellular ions during diseases or injuries may lead to uncontrolled neurotransmitter release independent on Ca²⁺ influx. However, its underlying molecular mechanism remains elusive. Here we show that elevation of the intracellular Zn²⁺ concentration leads to the increased frequency of spontaneous neurotransmitter release in hippocampal neurons. In the reconstituted system with neuronal SNAREs and Syt1, Zn²⁺ markedly enhances the fusion efficie

SUBMITTER: Xiang Y 

PROVIDER: S-EPMC12318101 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature