双孔通道家族与钙信号调节-潘丹

ISSN1007-7626CN11-3870/Qhttp//cjbmb．bjmu．edu．cnChineseJournalofBiochemistryandMolecularBiology20156316586～591··DOI10.13865/j．cnki．cjbmb．2015.06.06*(，410016;，410016)(Ca2+)．Ca2+(［Ca2+］i)、．，(nicotinicacidadeninedinucleotidephosphate，NAADP)Ca2+，．，(twoporechannels，TPCs)．TPCs，TPCs．;;;Q2Q26Q41Two-poreChannelsintheRegulationofCa2+SignalPANDanJIANGYong-LiangDAIAi-Guo*HunanProvinceGeriatricHospitalofNanhuaUniversityChangsha410016DepartmentofRespiratoryMedicineHunanInstituteofGerontologyChangsha410016ChinaAbstractCalciumionsplayanimportantroleinthephysiologicalactivitiesofcells．ThechangesofcalciumionCa2+concentrationiscloselyrelatedwithcellfunctionsignaltransductiontissuedamage/repairandapoptosis．IthasbeenknownthatnicotinicacidadeninedinucleotidephosphateNAADPisaneffectiveactivatorforthereleaseofintracellularCa2+butthemechanismisstillunclear．Recentstudieshavefoundthattwo-porechannelsTPCsmightbeinvolved．ThisreviewsummarizedtheresearchprogressaboutthestructureandfunctionofTPCsaswellasvariousphysiologicalandpathologicalcorrelatedeffects．ItprovidedusefulinformationforfurtherandbetterunderstandingofthephysiologicalfunctionsofTPCs．Keywordstwo-porechannelsTPCscalciumionCa2+nicotinicacidadeninedinucleotidephosphateNAADPsignalingpathway2014-09-162014-12-03No．81370153*[e-mail]162014AcceptedDecember32014SupportedbyNationalNaturalScienceFoundationofChinaNo．81370153*[e-mail]-porechannelsTPCsCa2+6．TPCs．TPCsNAADPCa2+Ca2+．、、．1TPCsLee1NAADP．NAADPβ-NADPNADP2．NADPCa2+NAADPCa2+3．Cancela4NAADPNAADP6Ca2+．NAADP．Hohenegger5、、、、NAADP．Navazio6NAADPCa2+．．IP3inositol145-trisphosphatecADPRcyclicadenosinediphosphateriboseCa2+NAADPCa2+．thapsigargin/sarco/endoplasmicreticulumS/ERATPCa2+Ca2+NAADPCa2+．NAADPCa2+A1bafilomycinA1．A1NAADPCa2+Ca2+．ATPCa2+．NAADPCa2+Ca2+NAADPCa2+7．-L--2-glycyl-L-phenylalanine-2-naphthylamideGPNNAADPCa2+IP3inositol145-trisphosphatereceptorsRyRryanodinereceptorsCa2+．NAADPCa2+Ca2+．TPCCa/Na8．NAADPNAADPZhu7NAADPIP3RsRyRsTPCsTPCNCa2+NAADP．TPC2NAADPCa2+Ca2+IP39．Ca2+TPCN2TPC2Ca2+TPCN2Ca2+Ca2+．TPCN2NAADPCa2+10TPCsTPC1TPC2NAADPCa2+11．2TPCsTPCs．6、13．12615、6163．TPC41NAADPFig．1．6transientreceptorpotentialTRPTPCsTPCsCa2+．TPCs46Ca2+8．TPC1、TPC2TPC/12．TPC2TPCN1TPCN2．TPC6TPC2．TPCNAADPCa2+11．TPC1TPCN1TPC3TPCN3．HEK2931TCP2．TPC2NAADP9．．TPC313．TPC1TPC2NAADPCa2+IP3RsCa2+TPC2．2TPC1TPC2TPC1．TPCTPC2PIP2Na+14．3TPCN．785311/3TPCN3TPCN3TPC3．1TPC3．TPCs．TPCNTPCN1．TPCN1TPCN3TPCN2．3TPCNsTPCN1TPCN3TPCNTPCs11Fig．2．NAADPTPC1H+Ca2+TPC1Ca2+15．TPC2NAADPpHNAADPTPC2pHTPC2pH16．NAADPIP3RsRyRsCa2+ER17．TPC1Ca2+TPC118．NAADPTPC19NAADPNAADP20．HAX-1TPCs21．Ned-19NAADPCa2+22．3TPCsTPCsNAADP．NAADPCa2+TPCCa2+．Ca2+．．NAADPS/ER．RyR100．“”NAADP11．“”60～10022．Ca2+．Ca2+NAADP23．ERCa2+Ca2+24．NAADP．TPCscalciuminducedcalciumreleaseCICRFig．3．TPC“”IP3Rs/RyRsERCICR7．NAADP/TPCCa2+．NAADP25．TPCsCa2+、．TPCsGTP．TPC226．TPC．NAADP/TPC2/pH．PC12NAADP27．TPC、．embryonicstemcellsESTPC2TPC2ES28．TPC2ES．TPC2ES．TPC227．HeLaESTPC2．TPC2NAADPNed-19．ATG5TPC229．Ca2+．TPCsNAADPCa2+30．CD38TPCsNAADPCa2+8856Fig．1Two-porechannelsrelationshipswithothervoltage-gatedchannelsandstructureorganizationAAphylogenetictreegeneratedbyClustalWhttp//align．genome．jpandplottedusingNeighbour-JoiningalgorithmforTPCsandselectedmembersofthesuperfamilyofvoltage-gatedchannels．ThesecondtransmembraneTMdomainofTPCsandthefourthTMdomainofCavandNavwerealignedwiththeTMdomainsincludingallsixTMsegmentsandtheporeloopofrepresentativeKvCNGTRPandCatSperchannels．BAsingleTPCsubunitcontains12putativeTMsegmentsthatcanbedividedintotwo6-TMhomologousdomainseachcontainingalsoaporeloopPloop．Basedonorientationofvoltage-gatedchannelstheaminoandcarboxylterminiaswellasthelargeloopinbetweenthetwodomainsareonthecytoplasmicsideoftheendolysosomalmembranes．RedbranchesindicateaputativeglycosylationsiteinhumanTPC2．C3-DprojectionmodelofanassembledTPCchannelwhichismostlikelyadimer3Fig．2SchematicdiagramdepictspartialfamilytreesfromtheanimalkingdomandidentifieskeyexamplesofspeciesinwhichthegenesencodingTPC1TPC2andTPC3areabsentorpresent“＞”denotespossiblepresenceofadditionalTPCs798531Fig．3Theproposedrolefortwo-porechannelsinintegrativeCa2+signalingFlowchartshowspathwaysforNAADPcADPRandIP3productionandtheireffectsonintracellularCa2+．ThedrawingsatthebottomdepictelementaryCa2+signalsgeneratedbyTPCsleftlightercolorandhigherpositionforhigherCa2+concentrationsandglobalCa2+signalsgeneratedbyactivatingIP3Rsand/orRyRsright．Reddashedlinesindicatealternativepathways．ThegreenpathwayontheleftshowsanalternativeconsequenceofTPC-mediatedCa2+release．ARCADP-ribosecyclaseincludingCD38PLCphospholipaseCmembranepotential．ICaCa2+currentthroughplasmamembrane11cADPRNAADPNAADP．CD38CD38mRNA31．33．IINOX2-ROSCD3831．TPCsNAADP12．TPCsNAADP34．Jha30TPC2Ca2+、．TPCsβ．34．．4TPCsTPCsTPCsTPCs．Ca2+TPCs．．References1LeeHCAarhusR．AderivativeofNADPmobilizescalciumstoresinsensitivetoinositoltrisphosphateandcyclicADP-riboseJ．JBiolChem27052152-21572GuseAHLeeHC．NAADPauniversalCa2+triggerJ．SciSignal2008144re103GalioneAEvansAMMaJe