Calpain 8nCL-2 and Calpain 9nCL-4 Constitute an Active Protease Complex, G-Calpain, Involved in Gastric Mucosal Defense 英文参考文献.docVIP

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Calpain 8nCL-2 and Calpain 9nCL-4 Constitute an Active Protease Complex, G-Calpain, Involved in Gastric Mucosal Defense 英文参考文献.doc

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Calpain 8nCL-2 and Calpain 9nCL-4 Constitute an Active Protease Complex, G-Calpain, Involved in Gastric Mucosal Defense 英文参考文献

Calpain8/nCL-2andCalpain9/nCL-4Constitutean ActiveProteaseComplex,G-Calpain,InvolvedinGastric MucosalDefense ShojiHata1,ManabuAbe2,HidenoriSuzuki3,FujikoKitamura1,NorikoToyama-Sorimachi4,KeikoAbe5, KenjiSakimura2,HiroyukiSorimachi1,6* 1CalpainProject,TheTokyoMetropolitanInstituteofMedicalScience(Rinshoken),Tokyo,Japan,2DepartmentofCellularNeurobiology,BrainResearchInstitute,Niigata University, Niigata, Japan, 3Laboratory of Electron Microscopy, The Tokyo Metropolitan Institute of Medical Science (Rinshoken), Tokyo, Japan, 4Department of Gastroenterology,NationalCenterforGlobalHealthandMedicine,Tokyo,Japan,5DepartmentofAgriculturalandLifeSciences,TheUniversityofTokyo,Tokyo,Japan, 6CoreResearchforEvolutionalScienceandTechnology(CREST),JapanScienceandTechnologyAgency(JST),Kawaguchi,Japan Abstract CalpainsconstituteasuperfamilyofCa2+-dependentcysteineproteases,indispensableforvariouscellularprocesses.Among the15mammaliancalpains,calpain8/nCL-2andcalpain9/nCL-4arepredominantlyexpressedinthegastrointestinaltractand arerestrictedtothegastricsurfacemucus(pit)cellsinthestomach.Possiblefunctionsreportedforcalpain8areinvesicle traffickingbetweenERandGolgi,andcalpain9areimplicatedinsuppressingtumorigenesis.Thesehighlightthatcalpains8 and9areregulateddifferentlyfromeachotherandfromconventionalcalpainsand,thus,havepotentiallyimportant,specific functionsinthegastrointestinaltract.However,thereisnodirectevidenceimplicatingcalpain8or9inhumandisease,and theirpropertiesandphysiologicalfunctionsarecurrentlyunknown.Toaddresstheirphysiologicalroles,weanalyzedmicewith mutationsinthegenesforthesecalpains,Capn8andCapn9.Capn82/2 andCapn92/2 micewerefertile,andtheirgastric mucosaeappearednormal.However,bothmiceweresusceptibletogastricmucosalinjuryinducedbyethanoladministration. Moreover,theCapn82/2stomachshowedsignificantdecreasesinbothcalpains9and8,andthesamewastrueforCapn92/2 . Consistentwiththisfinding,inthewild-typestomach,calpains8and9formedacomplexwetermed‘‘G-calpain,’’inwhich b