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Differential Subcellular Localization of the Splice Variants of the Zinc Transporter ZnT5 Is Dictated by the Different C-Terminal Regions

Lookup NU author(s): Dr Jared Thornton, Professor Dianne Ford, Professor Ruth Valentine



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 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). Conclusions: We thus propose that exons 15 to 17 include a signal that results in trafficking of ZnT5 to the Golgi apparatus and that the 39 end of exon 14 includes a signal that leads to retention in the ER.

Publication metadata

Author(s): Thornton JK, Taylor KM, Ford D, Valentine RA

Publication type: Article

Publication status: Published

Journal: PLoS One

Year: 2011

Volume: 6

Issue: 8

Print publication date: 01/08/2011

Date deposited: 05/01/2012

ISSN (print): 1544-9173

ISSN (electronic): 1932-6203

Publisher: Public Library of Science


DOI: 10.1371/journal.pone.0023878


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Funder referenceFunder name
BB/F019637/1UK Biotechnology and Biological Sciences Research Council
BBD01669X/2UK Biotechnology and Biological Sciences Research Council