The ZIP3 Zinc Transporter Is Localized to Mossy Fiber Terminals and Is Required for Kainate-Induced Degeneration of CA3 Neurons.

Tight regulation of neuronal Zn is critical for physiological function. Multiple Zn transporters are expressed in the brain, yet their spatial distribution and distinct roles are largely unknown. Here, we show developmental regulation of the expression of Zn transporters ZIP1 and ZIP3 in mouse hippocampal neurons, corresponding to previously described increase in neuronal vesicular Zn during the first postnatal month.

SNAP23 regulates KCC2 membrane insertion and activity following mZnR/GPR39 activation in hippocampalneurons.

Modulation of the neuronal K/Cl cotransporter 2 (KCC2) activity, which mediates Cl export, is critical to neuronal function. Here, we demonstrate that KCC2 interacts with the SNARE protein synaptosome-associated protein 23, SNAP23, an essential component of membrane insertion machinery. Using KCC2 truncated mutants, we show that KCC2 C-terminal domain is essential for membrane targeting and SNAP23-dependent upregulation of KCC2 activity triggered by activation of the Zn-sensitive receptor mZnR/GPR39 in HEK293 cells.

ZnT1 is a neuronal Zn/Ca exchanger.

Zinc transporter 1 (ZnT1; SLC30A1) is present in the neuronal plasma membrane, critically modulating NMDA receptor function and Zn neurotoxicity. The mechanism mediating Zn transport by ZnT1, however, has remained elusive. Here, we investigated ZnT1-dependent Zn transport by measuring intracellular changes of this ion using the fluorescent indicator FluoZin-3.