differential subcellular localization of the splice variants of the zinc transporter znt5 is dictated by the different c-terminal regions微分锌转运蛋白的亚细胞定位的剪接变体znt5是由不同的c端区域.pdfVIP

Differential Subcellular Localization of the Splice Variants of the Zinc Transporter ZnT5 Is Dictated by the Different C-Terminal Regions 1,2 4 1,3 1,2 Jared K. Thornton , Kathryn M. Taylor , Dianne Ford , Ruth A. Valentine * 1The Human Nutrition Research Centre, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, United Kingdom, 2 School of Dental Sciences, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, United Kingdom, 3 Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, United Kingdom, 4 Tenovus Cancer Research Centre, Welsh School of Pharmacy, Cardiff University, Cardiff , United Kingdom Abstract Background: 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. Principal Findings: 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 59 and 39 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