Dictyostelium discoideum Nucleoside Diphosphate Kinase C Plays a Negative Regulatory Role in Phagocytosis, Macropinocytosis and Exocytosis 英文参考文献.docVIP

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Dictyostelium discoideum Nucleoside Diphosphate Kinase C Plays a Negative Regulatory Role in Phagocytosis, Macropinocytosis and Exocytosis 英文参考文献.doc

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Dictyostelium discoideum Nucleoside Diphosphate Kinase C Plays a Negative Regulatory Role in Phagocytosis, Macropinocytosis and Exocytosis 英文参考文献

DictyosteliumdiscoideumNucleosideDiphosphate KinaseCPlaysaNegativeRegulatoryRolein Phagocytosis,MacropinocytosisandExocytosis SarahJ.Annesley1,RuzicaBago1,2,MajaHerakBosnar2,VedranaFilic3,MajaMarinovic′3,IgorWeber3, AnilMehta4,PaulR.Fisher1* 1DepartmentofMicrobology,LaTrobeUniversity,Victoria,Australia,2DivisionofMolecularMedicine,RudjerBosˇkovic′Institute,Zagreb,Croatia,3DivisionofMolecular Biology,RudjerBosˇkovic′Institute,Zagreb,Croatia,4DivisionofMedicalSciences,NinewellsHospitalandMedicalSchool,UniversityofDundee,Dundee,UnitedKingdom Abstract Nucleosidediphosphatekinases(NDPKs)areubiquitousphosphotransferenzymesresponsibleforproducingmostofthe nucleoside triphosphates except for ATP. This role is important for the synthesis of nucleic acids and proteins and the metabolism of sugars and lipids. Apart from this housekeeping role NDPKs have been shown to have many regulatory functions in diverse cellular processes including proliferation and endocytosis. Although the protein has been shown to have a positive regulatory role in clathrin- and dynamin-mediated micropinocytosis, its roles in macropinocytosis and phagocytosis havenotbeenstudied. The additionalnon-housekeepingroles ofNDPK areoftenindependent ofenzyme activitybutdependentontheexpressionleveloftheprotein.InthisstudywealteredtheexpressionlevelofNDPKinthe modeleukaryoticorganismDictyosteliumdiscoideumthroughantisenseinhibitionandoverexpression.Wedemonstratethat NDPKlevelsaffectgrowth,endocytosisandexocytosis.InparticularwefindthatDictyosteliumNDPKnegativelyregulates endocytosis in contrast to the positive regulatory role identified in higher eukaryotes. This can be explained by the differencesintypesofendocytosisthathavebeenstudiedinthedifferentsystems-phagocytosisandmacropinocytosisin Dictyosteliumcomparedwithmicropinocytosisinmammaliancells.ThisisthefirstreportofaroleforNDPKinregulating macropinocytosisandphagocytosis,theformerbeingthemajorfluidphaseuptakemechanismformacrophages,dendritic cellsandothe