Disease relevance of Slc30a3

• ZnT-3 reactivity was also present in the outer plexiform, inner nuclear, inner plexiform, and ganglion cell layers [1].

Psychiatry related information on Slc30a3

• Dissociation of synaptic zinc level and zinc transporter 3 expression during postnatal development and after sensory deprivation in the barrel cortex of mice [2].

High impact information on Slc30a3

• In mocha brain, the ZnT-3 transporter is reduced, resulting in a lack of zinc-associated Timm historeactivity in hippocampal mossy fibers [3].
• To specifically examine the role of synaptic zinc in the plaque accumulation, Tg2576 (also called APP2576) transgenic mice (hAPP(+)) expressing cerebral amyloid plaque pathology were crossed with mice lacking zinc transporter 3 (ZnT3(-/-)), which is required for zinc transport into synaptic vesicles [4].
• The mammalian protein ZnT3 resides on synaptic vesicle membranes of zinc-containing neurons, suggesting its possible role in vesicular zinc transport [5].
• Zinc transporter-3 (ZnT-3), a member of a growing family of mammalian zinc transporters, is expressed in regions of the brain that are rich in histochemically reactive zinc (as revealed by the Timm's stain), including entorhinal cortex, amygdala, and hippocampus [6].
• A membrane fraction enriched in vesicles containing the adaptor protein (AP) -3 cargo zinc transporter 3 was generated from PC12 cells and was used to identify new components of these organelles by mass spectrometry [7].

Biological context of Slc30a3

• During embryogenesis and early postnatal stages, ZnT3 transcripts were detected in several areas [8].
• After 10 and 30 days, however, downregulation of ZnT3 was paralleled by a distinct reduction in ZnSeAMG staining [9].

Anatomical context of Slc30a3

• ZnT3-/- mice, which lack histochemically reactive zinc in synaptic vesicles, had slightly higher thresholds to seizures elicited by the GABA(A) antagonist, bicuculline, and no differences in seizure threshold were seen in response to pentylenetetrazol or flurothyl [10].
• ZnT3 immunostaining was found in vesicle membranes in the apical part of the cells, associated to the microvillus membrane [11].
• Traceable zinc ions were also found in lysosome-like organelles of fenestrated endothelial cells, but here no corresponding ZnT3 immunostaining was seen [11].
• Developmental expression of ZnT3 in mouse brain: correlation between the vesicular zinc transporter protein and chelatable vesicular zinc (CVZ) cells. Glial and neuronal CVZ cells interact [8].
• We took advantage of zinc transporter 3 knockout mice, which lack vesicular zinc, to study the possible physiological role of this heavy metal in hippocampal mossy fiber neurotransmission [12].

Associations of Slc30a3 with chemical compounds

• Furthermore, compared with zinc transporter 3 (Znt3)-null mice, Znt3/Mt3 double-null mice exhibited further reductions in neuronal death in CA1 following kainate-induced seizures [13].
• The hippocampi of ZnT3-/- mice showed typical seizure-related neuronal damage in response to kainic acid, demonstrating that damage to the targets of zinc-containing neurons can occur independently of synaptically released zinc [10].
• Furthermore, neither amplitude nor duration of pharmacologically isolated N-methyl-D-aspartate, non-N-methyl-D-aspartate, GABA(A), and GABA(B) receptor-mediated postsynaptic potentials differed between zinc transporter 3 knockout and wild-type mice [12].
• However, mRNA levels of the delta subunit of adaptor protein complex (AP)-3, which modulates the level of Znt3 levels, were altered by estrogen depletion or replacement [14].
• Studies of the central nervous system have localized the zinc-transporter-3 (ZnT-3) protein to synaptic vesicles containing glutamate and zinc [1].

Other interactions of Slc30a3

• To determine the net effects of vesicular zinc release in the brain in vivo, we examined seizure susceptibility and seizure-related neuronal damage in mice with targeted disruption of the gene encoding the zinc transporter, ZnT3 (ZnT3-/- mice) [10].
• VAChT-positive preganglionic neurons were found to terminate on ZnT3 neuronal somata [15].
• It is therefore concluded that ZnT3 and zinc ions are present in a subpopulation of TH-positive, NPY-negative neurons in the rodent SCG, supporting the notion that vesicular zinc ions may play a special role in the peripheral sympathetic adrenergic system [15].
• While mh mice show a severe reduction of vesicular zinc (TIMM staining) owing to mislocalization and degradation of the Zinc transporter ZnT-3, the TIMM and ZnT-3 staining patterns in mh(2J) varies, with normal expression in hippocampal mossy fibers, but abnormal patterns in neocortex [16].
• These results suggest that in the barrel cortex ZnT3, synapsin I or synaptophysin are not determinant for the activity-dependent regulation of the synaptic zinc level [2].

Analytical, diagnostic and therapeutic context of Slc30a3

• The total protein concentration of ZnT3 was reduced by about 53%, and the total zinc concentration in the hippocampus of the same mice was reduced by 43-64%, 30 days after the adrenalectomy [9].
• Intraperitoneal injection of kainate induced seizures to a similar degree in wild type and ZnT3-null mice [17].
• We show here by electron microscopy that ZnT-3 decorates the membranes of all clear, small, round synaptic vesicles (SVs) in the mossy fiber boutons of both mouse and monkey [6].
• We examined the effects of ovariectomy and estrogen supplement on the levels of synaptic zinc and zinc transporter protein Znt3 in the brain [14].
• Western blots revealed that Znt3 levels in the brain were modulated in parallel with synaptic zinc levels, whereas no change was detected in the levels of Znt3 mRNA, as determined by Northern blot and reverse transcriptase-PCR analysis [14].

References