Chimaerin Suppresses Rac1 Activation at the Apical Membrane to Maintain the Cyst Structure.docVIP

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Chimaerin Suppresses Rac1 Activation at the Apical Membrane to Maintain the Cyst Structure.doc

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Chimaerin Suppresses Rac1 Activation at the Apical Membrane to Maintain the Cyst Structure

ChimaerinSuppressesRac1ActivationattheApical MembranetoMaintaintheCystStructure ShunsukeYagi1,MichiyukiMatsuda1,2,EtsukoKiyokawa2,3 * 1LaboratoryofBioimagingandCellSignaling,GraduateSchoolofBiostudies,KyotoUniversity,YoshidaKonoe-cho,Sakyo-ku,Kyoto,Japan,2DepartmentofPathology andBiologyofDiseases,GraduateSchoolofMedicine,KyotoUniversity,YoshidaKonoe-cho,Sakyo-ku,Kyoto,Japan,3DepartmentofOncologicPathology,Kanazawa MedicalUniversity,Uchinada,Kahoku-gun,Ishikawa,Japan Abstract Epithelialorgansaremadeofawell-polarizedmonolayerofepithelialcells,andtheirmorphologyismaintainedstrictlyfor their proper functions. Previously, we showed that Rac1 activation is suppressed at the apical membrane in the mature organoid,andthatsuchspatiallybiasedRac1activityisrequiredforthepolaritymaintenance.HereweidentifyChimaerin, aGTPaseactivatingproteinforRac1,asasuppressorofRac1activityattheapicalmembrane.DepletionofChimaerincauses over-activationofRac1attheapicalmembraneinthepresenceofhepatocytegrowthfactor(HGF),followedbyluminalcell accumulation. Importantly, Chimaerin depletion did not inhibit extension formation at the basal membrane. These observationssuggestthatChimaerinfunctionsastheapical-specificRac1GAPtomaintainepithelialmorphology. Citation:YagiS,MatsudaM,KiyokawaE(2012)ChimaerinSuppressesRac1ActivationattheApicalMembranetoMaintaintheCystStructure.PLoSONE7(12): e52258.doi:10.1371/journal.pone.0052258 Editor:EdManser,Astar-NeuroscienceResearchPartnership(NRP)andInstituteofMedicalBiology(IMB),Singapore ReceivedAugust15,2012;AcceptedNovember9,2012;PublishedDecember20,2012 Copyright:?2012Yagietal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermitsunrestricted use,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding: This work was supported by grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. S. Yagi was supported by research fellowships from the Japan S