Palmiter R D, Cole T B, Quaife C J, Findley S D
Howard Hughes Medical Institute, University of Washington, Seattle 98195, USA.
Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14934-9. doi: 10.1073/pnas.93.25.14934.
The murine ZnT3 gene was cloned by virtue of its homology to the ZnT2 gene, which encodes a membrane protein that facilitates sequestration of zinc in endosomal vesicles. ZnT-3 protein is predicted to have six transmembrane domains and shares 52% amino acid identity with ZnT-2, with the homology extending throughout the two sequences. Human ZnT-3 cDNAs were also cloned; the amino acid sequence is 86% identical to murine ZnT-3. The mouse ZnT3 gene has 8 exons and maps to chromosome 5. Northern blot and reverse transcriptase-PCR analyses demonstrate that murine ZnT-3 expression is restricted to the brain and testis. In situ hybridization reveals that within the brain, ZnT-3 mRNA is most abundant in the hippocampus and cerebral cortex. Antibodies raised against the C-terminal tail of mouse ZnT-3 react with the projections from these neurons and produce a pattern similar to that obtained with Timm's reaction, which reveals histochemically reactive zinc within synaptic vesicles. We propose that ZnT-3 facilitates the accumulation of zinc in synaptic vesicles.
小鼠锌转运体3（ZnT3）基因是依据其与锌转运体2（ZnT2）基因的同源性克隆得到的，ZnT2基因编码一种膜蛋白，该蛋白有助于将锌隔离在内体小泡中。预测ZnT-3蛋白有6个跨膜结构域，与ZnT-2有52%的氨基酸同一性，这种同源性贯穿于这两个序列。人类ZnT-3的cDNA也被克隆出来了；其氨基酸序列与小鼠ZnT-3有86%的同一性。小鼠ZnT3基因有8个外显子，定位于5号染色体。Northern印迹法和逆转录聚合酶链反应分析表明，小鼠ZnT-3的表达仅限于脑和睾丸。原位杂交显示，在脑中，ZnT-3 mRNA在海马体和大脑皮层中最为丰富。针对小鼠ZnT-3 C末端尾巴产生的抗体与这些神经元的突起发生反应，产生的模式类似于用Timm反应得到的模式，Timm反应可在突触小泡中显示组织化学反应性锌。我们认为ZnT-3促进锌在突触小泡中的积累。
