Endocytosis of the Anthrax Toxin Is Mediated by Clathrin, Actin and Unconventional Adaptors 英文参考文献.docVIP

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Endocytosis of the Anthrax Toxin Is Mediated by Clathrin, Actin and Unconventional Adaptors 英文参考文献.doc

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Endocytosis of the Anthrax Toxin Is Mediated by Clathrin, Actin and Unconventional Adaptors 英文参考文献

EndocytosisoftheAnthraxToxinIsMediatedby Clathrin,ActinandUnconventionalAdaptors LaurenceAbrami,MirkoBischofberger,Be′atriceKunz,RomainGroux,F.GisouvanderGoot* GlobalHealthInstitute,EcolePolytechniqueFe′de′rale deLausanne,FacultyofLifeSciences,Lausanne,Switzerland Abstract Theanthraxtoxinisatripartitetoxin,wherethetwoenzymaticsubunitsrequirethethirdsubunit,theprotectiveantigen (PA),tointeractwithcellsandbeescortedtotheircytoplasmictargets.PAbindstocellsviaoneoftworeceptors,TEM8and CMG2.Interestingly,thetoxintimesandtriggersitsownendocytosis,inparticularthroughtheheptamerizationofPA.Here weshowthatPAtriggerstheubiquitinationofitsreceptorsinab-arrestin-dependentmannerandthatthisstepisrequired forclathrin-mediatedendocytosis.Inaddition,wefindthatendocytosisisdependentontheheterotetramericadaptorAP-1 butnotthemoreconventionalAP-2.Finally,weshowthatendocytosisofPAisstronglydependentonactin.Unexpectedly, actinwasalsofoundtobeessentialforefficientheptamerizationofPA,butonlywhenboundtooneofits2receptors, TEM8, due to the active organization of TEM8 into actin-dependent domains. Endocytic pathways are highly modular systems. Herewe identify some of the key players that allow efficient heptamerization of PA andsubsequent ubiquitin- dependent,clathrin-mediatedendocytosisoftheanthraxtoxin. Citation: Abrami L, Bischofberger M, Kunz B, Groux R, van der Goot FG (2010) Endocytosis of the Anthrax Toxin Is Mediated by Clathrin, Actin and UnconventionalAdaptors.PLoSPathog6(3):e1000792.doi:10.1371/journal.ppat.1000792 Editor:JohnA.T.Young,TheSalkInstituteforBiologicalStudies,UnitedStatesofAmerica ReceivedJuly10,2009;AcceptedJanuary26,2010;PublishedMarch5,2010 Copyright: ? 2010 Abrami et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:ThisworkwassupportedbytheSwissNationalScienceFoundation,theFondati