ZnT3mediated

ZnT3-mediated refers to processes that depend on the zinc transporter ZnT3, a member of the SLC30 family responsible for transporting zinc into intracellular compartments. ZnT3, encoded by the SLC30A3 gene, loads zinc into synaptic vesicles of select neurons, enabling activity-dependent release of zinc into the synaptic cleft and extracellular space. This vesicular zinc can act as a neuromodulator, influencing neurotransmission and intracellular signaling.

ZnT3 is concentrated in brain regions involved in learning and memory, with high expression in glutamatergic circuits such as the hippocampus, cortex, and limbic structures, including mossy fiber terminals in the dentate gyrus. Its distribution supports a role for ZnT3-mediated zinc signaling in synaptic modulation within these networks.

Mechanistically, ZnT3 operates as a zinc/proton antiporter, loading zinc from the cytosol into synaptic vesicles by utilizing the vesicle proton gradient. Zinc is released by exocytosis during vesicle fusion and can modulate postsynaptic receptors and synaptic plasticity, contributing to activity-dependent signaling dynamics.

Physiological and clinical relevance: ZnT3-mediated zinc signaling participates in regulation of synaptic plasticity, including long-term potentiation, and in certain forms of memory. In mice lacking ZnT3, vesicular zinc is abolished and hippocampal plasticity and memory performance can be impaired, making this model informative for studying zinc’s neuromodulatory roles. Dysregulation of ZnT3 or vesicular zinc has been discussed in aging and neurodegenerative disease models.

Research approaches include genetic knockout models, zinc imaging probes, and pharmacological tools to modulate ZnT3 activity, which help illuminate zinc’s role in synaptic function and potential therapeutic strategies for disorders involving metal dyshomeostasis.