SLC30A3

SLC30A3, also known as ZNT3, is a gene in the solute carrier family 30 that encodes the zinc transporter protein ZnT3. ZnT3 is a member of the Cation Diffusion Facilitator (CDF) family and is primarily expressed in the brain. The protein functions as a membrane transporter that moves zinc ions (Zn2+) from the cytosol into synaptic vesicles.

In neurons, ZnT3 localizes mainly to presynaptic terminals and is enriched in regions such as the hippocampus and cortex. By loading synaptic vesicles with Zn2+, ZnT3 enables activity-dependent co-release of zinc with neurotransmitters. Vesicular zinc serves as a neuromodulator that can influence signaling through various neurotransmitter receptors and can modulate synaptic plasticity, learning, and memory processes.

Structurally, ZnT3 is predicted to contain multiple transmembrane domains typical of the ZnT/Slc30 family, with cytosolic regions that participate in regulation and trafficking. The transporter relies on the proton motive force to drive zinc sequestration into vesicles.

Genetic and functional studies in mice have shown that loss of ZnT3 eliminates vesicular zinc in several brain regions and can lead to altered synaptic plasticity and certain learning and memory deficits. In humans, variants in SLC30A3 have been explored for associations with neurodegenerative and cognitive conditions, but no single causative mutation has been confirmed.

Overall, SLC30A3 plays a central role in brain zinc homeostasis by mediating neuronal vesicular zinc loading, with implications for synaptic function and cognitive processes.