Differential Subcellular Localization of the Splice Variants of the Zinc Transporter ZnT5 Is Dictated by the Different C-Terminal Regions 英文参考文献.docVIP

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Differential Subcellular Localization of the Splice Variants of the Zinc Transporter ZnT5 Is Dictated by the Different C-Terminal Regions 英文参考文献.doc

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Differential Subcellular Localization of the Splice Variants of the Zinc Transporter ZnT5 Is Dictated by the Different C-Terminal Regions 英文参考文献

DifferentialSubcellularLocalizationoftheSplice VariantsoftheZincTransporterZnT5IsDictatedbythe DifferentC-TerminalRegions JaredK.Thornton1,2,KathrynM.Taylor4,DianneFord1,3,RuthA.Valentine1,2 * 1TheHumanNutritionResearchCentre,InstituteforCellandMolecularBiosciences,NewcastleUniversity,NewcastleuponTyne,UnitedKingdom, 2SchoolofDental Sciences, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, United Kingdom, 3Institute for Cell and Molecular Biosciences, NewcastleUniversity,NewcastleuponTyne,UnitedKingdom,4TenovusCancerResearchCentre,WelshSchoolofPharmacy,CardiffUniversity,Cardiff,UnitedKingdom Abstract Background:Zincisemergingasanimportantintracellularsignalingmolecule,aswellasfulfillingessentialstructuraland catalyticfunctionsthroughincorporationinamyriadofzincmetalloproteinssoitisimportanttoelucidatethemolecular mechanismsofzinchomeostasis,includingthesubcellularlocalizationsofzinctransporters. Principal Findings: Two splice variants of the human SLC30A5 Zn transporter gene (ZnT5) have been reported in the literature.ThesevariantsdifferattheirN-andC-terminalregions,correspondingwiththeuseofdifferent59and39exons. We demonstrate that full length human ZnT5 variant B is a genuine transcript in human intestinal cells and confirm expressionofbothvariantAandvariantBinarangeofuntreatedhumantissuesbysplicevariant-specificRT-PCR.UsingN- orC-terminalGFPorFLAGfusionsofbothisoformsofZnT5weidentifythatthedifferentialsubcellularlocalizationtothe Golgi apparatus and ER respectively is a function of their alternative C-terminal sequences. These different C-terminal regionsresultfromtheincorporationintothematuretranscriptofeitherthewholeofexon14(variantB)oronlythe59 regionofexon14plusexons15–17(variantA). Conclusions:Wethusproposethatexons15to17includeasignalthatresultsintraffickingofZnT5totheGolgiapparatus andthatthe39endofexon14includesasignalthatleadstoretentionintheER. Citation:ThorntonJK,TaylorKM,FordD,ValentineRA(2011)Diffe