Molecular Model of the Microvillar Cytoskeleton and Organization of the Brush Border 英文参考文献.docVIP

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Molecular Model of the Microvillar Cytoskeleton and Organization of the Brush Border 英文参考文献.doc

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Molecular Model of the Microvillar Cytoskeleton and Organization of the Brush Border 英文参考文献

MolecularModeloftheMicrovillarCytoskeletonand OrganizationoftheBrushBorder JeffreyW.Brown,C.JamesMcKnight* DepartmentofPhysiologyandBiophysics,BostonUniversitySchoolofMedicine,Boston,Massachusetts,UnitedStatesofAmerica Abstract Background:Brushbordermicrovilliare,1-mmlongfinger-likeprojectionsemanatingfromtheapicalsurfacesofcertain, specializedabsorptiveepithelialcells.Ahighlysymmetrichexagonalarrayofthousandsoftheseuniformlysizedstructures form the brush border, which in addition to aiding in nutrient absorption also defends the large surface area against pathogens. Here, we present a molecular model of the protein cytoskeleton responsible for this dramatic cellular morphology. Methodology/Principal Findings: The model is constructed from published crystallographic and microscopic structures reportedbyseveralgroupsoverthelast30+years.Oureffortsresultedinasingle,unique,self-consistentarrangementof actin,fimbrin,villin,brushbordermyosin(Myo1A),calmodulin,andbrushborderspectrin.Thecentralactincorebundlethat supportsthemicrovillusisnearlysaturatedwithfimbrinandvillincross-linkersandhasadensitysimilartothatfoundin protein crystals. The proposed model accounts for all major proteinaceous components, reproduces the experimentally determinedstoichiometry,andisconsistentwiththesizeandmorphologyofthebiologicalbrushbordermembrane. Conclusions/Significance:Themodelpresentedherewillserveasastructuralframeworktoexplainmanyofthedynamic cellularprocessesoccurringoverseveraltimescales,suchasproteindiffusion,association,andturnover,lipidraftsorting, membrane deformation, cytoskeletal-membrane interactions, and even effacement of the brush border by invading pathogens. In addition, this model provides a structural basis for evaluating the equilibrium processes that result in the uniformsizeandstructureofthehighlydynamicmicrovilli. Citation: Brown JW, McKnight CJ (2010) Molecular Model of the Microvillar Cytoskeleton and Organization of the Brush Border. PLoS ONE 5(2): e9406. doi:10