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1、TheJournalofNeuroscience,June24,2009•29(25):8063–8074•8063Cellular/Molecular2CaRegulationofDynamin-IndependentEndocytosisinCorticalAstrocytesMinJiangandGongChenDepartmentofBiology,HuckInstitutesofLifeSciences,ThePennsylvaniaStateUniversity,UniversityPark,Pennsylvania16802AstrocytesreleaseAT
2、Pandglutamatethroughvesicularexocytosistomediateneuron–glialinteractions.Incontrasttoexocytosis,theendocyticpathwaysinastroglialcellsarepoorlyunderstood.Here,weidentifyaconstitutiveendocyticpathwayinculturedastrocytesthatisdependentonneitherclathrinnordynamin.Thisdynamin-independentendocytic
3、pathwayisregulatedbyRab5,anearlyendo-someprotein.Theendocytosedvesiclesshowfasttransitionfromearlyendosomestolateendosomesandlysosomeswithinafew2minutes.Interestingly,thisclathrin-anddynamin-independentendocytosisinastrocytesispotentlyregulatedbyintracellularCa.2ATPandglutamategreatlyenhan
4、cethedynamin-independentendocytosisthroughelevatingtheintracellularCa.Inaddition,2amyloid-peptide(A)alsoenhancesthedynamin-independentendocytosisbyinducingCatransientsinastrocytes.Theseresults2demonstrateanovelendocyticpathwayinglialcellsthatisdynaminindependentbuttightlyregulatedbyintra
5、cellularCa.TheregulationbyATP,glutamate,andAsuggestsanimportantroleofthedynamin-independentendocytosisinbothphysiologicalandpathologicalconditions.IntroductionandHelenius,2002;Thomsenetal.,2002).Bothclathrin-andEndocytosisisafundamentalcellularfunctioninvolvedinnutri-caveolin-mediatedendocy
6、tosisaredependentonaGTPaseentuptake,pathogenremoval,andtransportingsignalingmole-dynamin,whichformsaringontheneckofinvaginatedpitsculesfromextracellularenvironmenttointracellularcytoplasm.afterinitialendocytosisandpinchesoffvesiclesfromtheEndocytosisincludesphagocytosis,whichinternalizeslarg
7、epar-plasmamembrane(Sever,2002).Incontrast,verylittleisticles,andpinocytosis,whichinternalizesmembraneproteins,knownaboutclathrin-andcaveolin-independentendocyto-lipids,andfluidwithsolublemolecules(ConnerandSchmid,sis,althoughsuchendocyticpathwayha