ZnTs

ZnTs, or zinc transporter proteins of the SLC30 family, are membrane proteins that move Zn2+ from the cytosol into intracellular organelles or out of the cell. This activity complements ZIP transporters (SLC39) and helps maintain cytosolic zinc homeostasis, preventing toxicity while supplying zinc for enzymes and signaling proteins.

The human ZnT family comprises multiple members (SLC30A1–A10). Most ZnTs function as Zn2+-selective antiporters that couple Zn2+ movement to proton or other cation gradients across membranes. Structural features include multiple transmembrane helices and cytosolic N- and C-terminal regions; a histidine-rich loop contributes to zinc binding in some members. Subcellular localization varies: ZnT1 at the plasma membrane reduces cytosolic Zn2+ by exporting it; ZnT2 and ZnT4–7 traffic to secretory compartments such as secretory granules, the Golgi complex, and the endoplasmic reticulum; ZnT3 concentrates Zn2+ in synaptic vesicles in certain neurons; ZnT8 localizes to insulin-containing secretory granules in pancreatic beta cells. By sequestering Zn2+ into these compartments, zinc is available for metalloproteins and regulated release.

Physiological and clinical relevance: Zinc transporters shape development, immune function, and neurotransmission. Genetic variants or dysregulation can affect zinc homeostasis. Notably, variants in SLC30A8 (ZnT8) are associated with type 2 diabetes risk. Mutations in SLC30A2 (ZnT2) can cause neonatal zinc deficiency with low breast-milk zinc. Animal studies highlight ZnT3’s role in zinc signaling for learning and memory.

In summary, ZnTs are essential components of cellular zinc management, balancing storage, secretion, and access to zinc for diverse biological processes.