Differential subcellular localization of the splice variants of the zinc transporter ZnT5 is dictated by the different C-terminal regions.
Differential subcellular localization of the splice variants of the zinc transporter ZnT5 is dictated by the different C-terminal regions.
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DOI：
10.1371/journal.pone.0023878
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Valentine RA
中科院分区：
文献类型：
--
作者：
Thornton JK;Taylor KM;Ford D;Valentine RA
锌是一种重要的细胞内信号分子，并通过与无数锌金属蛋白结合来实现必要的结构和催化功能，因此阐明锌稳态的分子机制，包括锌转运蛋白的亚细胞定位是很重要的。文献报道了人类SLC30A5锌转运基因（ZnT5）的两个剪接变体。这些变异在它们的N端和c端区域不同，对应于使用不同的5 ‘和3 ’外显子。我们通过剪接变异特异性RT-PCR证实了ZnT5全长变异B在人肠细胞中是一个真正的转录本，并证实了变异a和变异B在一系列未经处理的人组织中都有表达。利用ZnT5两种亚型的N端或c端GFP或FLAG融合，我们发现高尔基体和内质网的亚细胞定位差异分别是它们的c端序列的作用。这些不同的c端区域是由于将整个外显子14（变体B）或仅将外显子14的5 '区域加上外显子15-17（变体A）整合到成熟转录本中造成的。因此，我们提出外显子15至17包含一个导致ZnT5运输到高尔基体的信号，外显子14的3 '端包含一个导致内质网保留的信号。
Zinc is emerging as an important intracellular signaling molecule, as well as fulfilling essential structural and catalytic functions through incorporation in a myriad of zinc metalloproteins so it is important to elucidate the molecular mechanisms of zinc homeostasis, including the subcellular localizations of zinc transporters. Two splice variants of the human SLC30A5 Zn transporter gene (ZnT5) have been reported in the literature. These variants differ at their N- and C-terminal regions, corresponding with the use of different 5′ and 3′ exons. We demonstrate that full length human ZnT5 variant B is a genuine transcript in human intestinal cells and confirm expression of both variant A and variant B in a range of untreated human tissues by splice variant-specific RT-PCR. Using N- or C-terminal GFP or FLAG fusions of both isoforms of ZnT5 we identify that the differential subcellular localization to the Golgi apparatus and ER respectively is a function of their alternative C-terminal sequences. These different C-terminal regions result from the incorporation into the mature transcript of either the whole of exon 14 (variant B) or only the 5′ region of exon 14 plus exons 15–17 (variant A). We thus propose that exons 15 to 17 include a signal that results in trafficking of ZnT5 to the Golgi apparatus and that the 3′ end of exon 14 includes a signal that leads to retention in the ER.
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