Distinct Roles of Plasmodium Rhomboid 1 in Parasite Development and Malaria Pathogenesis 英文参考文献.docVIP

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Distinct Roles of Plasmodium Rhomboid 1 in Parasite Development and Malaria Pathogenesis 英文参考文献.doc

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Distinct Roles of Plasmodium Rhomboid 1 in Parasite Development and Malaria Pathogenesis 英文参考文献

DistinctRolesofPlasmodiumRhomboid1inParasite DevelopmentandMalariaPathogenesis PrakashSrinivasan¤*,IsabelleCoppens,MarceloJacobs-Lorena MalariaResearchInstituteandDepartmentofMolecularMicrobiologyandImmunology,JohnsHopkinsSchoolofPublicHealth,Baltimore,Maryland,UnitedStatesof America Abstract Invasionofhostcellsbythemalariaparasiteinvolvesrecognitionandinteractionwithcell-surfacereceptors.Awidevariety ofparasitesurfaceproteinsparticipateinthisprocess,mostofwhicharespecifictotheparasite’sparticularinvasiveform. Upon entry, the parasite has to dissociate itself from the host-cell receptors. One mechanism by which it does so is by shedding its surface ligands using specific enzymes. Rhomboid belongs to a family of serine proteases that cleave cell- surface proteins within their transmembrane domains. Here we identify and partially characterize a Plasmodium berghei rhomboid protease (PbROM1) that plays distinct roles during parasite development. PbROM1 localizes to the surface of sporozoites after salivary gland invasion. In blood stage merozoites, PbROM1 localizes to the apical end where proteins involvedininvasionarealsopresent.OurgeneticanalysissuggeststhatPbROM1functionsintheinvasivestagesofparasite development.Whereaswild-typeP.bergheiislethaltomice,animalsinfectedwithPbROM1nullmutantscleartheparasites efficiently and develop long-lasting protective immunity. The results indicate that P. berghei Rhomboid 1 plays a nonessential but important role during parasite development and identify rhomboid proteases as potential targets for diseasecontrol. Citation:SrinivasanP,CoppensI,Jacobs-LorenaM(2009)DistinctRolesofPlasmodiumRhomboid1inParasiteDevelopmentandMalariaPathogenesis.PLoS Pathog5(1):e1000262.doi:10.1371/journal.ppat.1000262 Editor:KirkDeitsch,WeillMedicalCollegeofCornellUniversity,UnitedStatesofAmerica ReceivedJune20,2008;AcceptedDecember12,2008;PublishedJanuary16,2009 Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsPublicDomaindeclaratio