Pyrin Modulates the Intracellular Distribution of PSTPIP1 英文参考文献.docVIP

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Pyrin Modulates the Intracellular Distribution of PSTPIP1 英文参考文献.doc

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Pyrin Modulates the Intracellular Distribution of PSTPIP1 英文参考文献

PyrinModulatestheIntracellularDistributionofPSTPIP1 AndreaL.Waite2.,PhilipSchaner1.,NeilRichards2,BanuBalci-Peynircioglu3,SethL.Masters4, SusannahD.Brydges5,MichelleFox2,ArthurHong2,EnginYilmaz3,DanielL.Kastner5,EllisL.Reinherz6, DeborahL.Gumucio2* 1Division of Radiology/Oncology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America, 2Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan, United States of America, 3Department of Medical Biology, Faculty of Medicine, Hacettepe University, Ankara, Turkey,4SchoolofBiochemistryandImmunology,TrinityCollege,Dublin,Ireland,5GeneticsandGenomicsBranch,NationalInstituteofArthritisandMusculoskeletaland SkinDisease,NationalInstitutesofHealth(NIH),Bethesda,Maryland,UnitedStatesofAmerica,6HarvardMedicalSchool,LaboratoryofImmunology,DanaFarberCancer Institute,Boston,Massachusetts,UnitedStatesofAmerica Abstract PSTPIP1 is a cytoskeleton-associated adaptor protein that links PEST-type phosphatases to their substrates. Mutations in PSTPIP1causePAPAsyndrome(PyogenicsterileArthritis,Pyodermagangrenosum,andAcne),anautoinflammatorydisease. PSTPIP1 binds to pyrin and mutations in pyrin result in familial Mediterranean fever (FMF), a related autoinflammatory disorder.Sincedisease-associatedmutationsinPSTPIP1enhancepyrinbinding,PAPAsyndromeandFMFarethoughtto shareacommonpathoetiology.ThestudiesoutlinedheredescribeseveralnewaspectsofPSTPIP1andpyrinbiology.We document that PSTPIP1, which has homology to membrane-deforming BAR proteins, forms homodimers and generates membrane-associatedfilamentsinnativeandtransfectedcells.AnextendedFCH(Fes-Cip4homology)domaininPSTPIP1is necessaryandsufficientforitsself-aggregation.WefurthershowthatthePSTPIP1filamentnetworkisdependentuponan intacttubulincytoskeletonandthatthedistributionofthisnetworkcanbemodulatedbypyrin,indicatingthatthisisa dynamicstructure.Finally,wedemonstratethatpyrincanrecruitPSTPIP1intoaggregations(specks)ofASC,anotherpy