1、SnapShot:Actin Regulators I Anosha D.Siripala and Matthew D.WelchDepartment of Molecular and Cell Biology,University of California,Berkeley,CA 94720,USAProtein FamilyBiochemical FunctionRepresentative ProteinsH.sapiensD.melanogasterC.elegansA.thalianaS.cerevisiaeActin NucleatorsForminsassociateswith
2、barbedends,promotesnucleation*hDia1,2,3,FHOD1,2,3,4,DAAM1,2,FMN1,2,FRL1,2,3,INF1,2,DelphilinDiaphanous/Dia,Cappucino/FMN,DAAM,FRL,FHOD,INFDia/CYK-1,DAAM,FRL,FHOD,INFAtFH1-4,5,6-21Bni1,Bnr1Spirnucleatesunbranchedfi lamentsSpir-1,Spir-2Spir/spireArp2/3 complexpolymerizesY-branchedfi lamentnetworksARP2
3、,ARP3,ARPC1A,1B,2,3,4,5,5LARP2,ARP3,ARPC1,2,3A,3B,4,5,5LARX1-7ARP2,ARP3,ARPC1-5Arp2,Arp3,Arc40,35,18,19,15Arp2/3 complex regulatorsCARMILlinkscappingprotein,Arp2/3andmyosinICARMILDCarmilQ21301CoroninbindsF-actinandArp2/3complex,enhancesactindepolymerizationcoronin1A,B,C;2A,B;7Coro/Coronin,Dpod1COR-1
4、,POD-1Crn1Cortactinactivates/modulatesArp2/3complex,bindsF-actincortactin,HS1DCortactinSCAR/WAVE familyactivatesArp2/3complexSCAR1,SCAR2,SCAR3SCARWVE-1AtSCAR1,2,3,4WASP familyactivatesArp2/3complex*WASP,N-WASPWASpWSP-1Las17/Bee1G-Actin Binding ProteinsCAP/Srv2recyclesactinmonomersCAP1,CAP2Actup/Capu
5、letCAS-1AtCAP1Srv2Profi linpromotesactinmonomeradditionatbarbedendsprofi lin1,2,3,4ChickadeePFN1,2,3PRF1-3(vegetative),PRF4-5(reproductive)Pfy1Thymosin 4sequestersG-actinthymosin4CiboulotTTH-1Verprolin/WIPbindsactinmonomers,WASPWIP,WIRE/WICH,CR16Q8MLU0WIP-1Vrp1F-Actin Binding ProteinsEna/VASP family
6、antagonizesCapZcappingatfi lamentends,recruitsprofi linMena,VASP,EVLEnabledUNC-34MIMbindsbothG-andF-actin,mayregulatenucleation-promotingfactorsMIMPointed End Capping ProteinsTropomodulin/Tmodcapspointedends,bindstropomyosinTmod1,2,3,4,Lmod1,2,3SanpodoTMD-1,TMD-2Barbed End Capping ProteinsAIP1promot
7、esdepolymerizationbyADF/cofi linAIP1/WDR1Aip1AIP-1/UNC-78AtAIP1Aip1CapGcapsbarbedends(calcium-dependent)capGCapGCapZ/capping protein/-actininheterodimercapsbarbedendscapZ(A1-3,B1-2)CapZ(cpa,cpb)CAP-1,CAP-2AtCPA,AtCPBCap1,Cap2Eps8capsbarbedends,involvedinRacsignallingEps8,Eps8L1,2,3Arouser,Q95TJ6EPS-
8、8Actin Depolymerizing/Severing ProteinsADF/cofi linpromotesactinfi lamentdisassemblycofi lin1,cofi lin2,ADFCofi lin/TwinstarUNC-60A,BAtADF1-12Cof1Gelsolin/villin superfamilyseversactinfi lamentsgelsolin,adseverin/scinderin,villin,advillin,supervillin,flightlessIGelsolin,Villin-like/Quail,FlightlessI
9、gelsolin(Q21253),supervillin(P91041),FLI-1VLN1-5Twinfi lininhibitsactinnucleotideexchange,seversactintwinfi lin-1/A6,twinfi lin-2Twinfi linU46668Twf1Actin Bundling/Crosslinking Proteins-actininconnectsandorganizesactinfi laments-actinin1-4-actinin/FlightlessAATN-1EPLINstabilizesandbundlesactinfi lam
10、entsEPLINEspinformsparallelactinbundles*espinForkedFascinbundlesactinfi lamentsfascin1,2,3SingedFilaminorthogonallycrosslinksactinfi lamentsfi lamin*A,*B,CJitterbug,CheerioQ18109Fimbrin/plastinbundlesactinfi lamentsplastin1-3(I,L,T)FimbrinQ965Y6AtFIM1Sac6Identifi ed Cellular Role:XMembranetraffi cki
11、ngandphagocytosisXCytokinesisXCellsurfaceorganizationanddynamicsXCelladhesionXMultiplefunctionsXOther/unknownUNIPROTdatabaseaccessionnumber*Mutationlinkedtohumandisease626 Cell128,February9,20072007ElsevierInc.DOI10.1016/j.cell.2007.02.001Seeonlineversionforreferencesandabbreviations.ActinRegulators
12、IIwillappearintheMarch9issueofCell.SnapShot:Actin Regulators I Anosha D.Siripala and Matthew D.WelchDepartment of Molecular and Cell Biology,University of California,Berkeley,CA 94720,USA626.e1 Cell128,February9,20072007ElsevierInc.DOI10.1016/j.cell.2007.02.001RefeRencesAspenstrom,P.(2005).Theverpro
13、linfamilyofproteins:Regulatorsofcellmorphogenesisandendocytosis.FEBSLett.579,52535259.Daly,R.J.(2004).Cortactinsignallinganddynamicactinnetworks.Biochem.J.382,1325.dosRemedios,C.G.,Chhabra,D.,Kekic,M.,Dedova,I.V.,Tsubakihara,M.,Berry,D.A.,andNosworthy,N.J.(2003).Actinbindingproteins:regulationofcyto
14、skeletalmicrofilaments.Physiol.Rev.83,433473.Goley,E.D.,andWelch,M.D.(2006).TheARP2/3complex:Anactinnucleatorcomesofage.Nat.Rev.Mol.CellBiol.7,713726.Higgs,H.N.,andPeterson,K.J.(2005).Phylogeneticanalysisoftheforminhomology2domain.Mol.Biol.Cell16,113.Kerkhoff,E.(2006).CellularfunctionsoftheSpiractin
15、-nucleationfactors.TrendsCellBiol.16,477483.Krause,M.,Dent,E.W.,Bear,J.E.,Loureiro,J.J.,andGertler,F.B.(2003).Ena/VASPproteins:Regulatorsoftheactincytoskeletonandcellmigration.Annu.Rev.CellDev.Biol.19,541564.Paavilainen,V.O.,Bertling,E.,Falck,S.,andLappalainen,P.(2004).Regulationofcytoskeletaldynami
16、csbyactin-monomer-bindingproteins.TrendsCellBiol.14,386394.Silacci,P.,Mazzolai,L.,Gauci,C.,Stergiopulos,N.,Yin,H.L.,andHayoz,D.(2004).Gelsolinsuperfamilyproteins:Keyregulatorsofcellularfunctions.Cell.Mol.LifeSci.61,26142623.Uetrecht,A.C.,andBear,J.E.(2006).Coronins:Thereturnofthecrown.TrendsCellBiol
17、.16,421426.AbbReviAtionsADF:actin-depolymerizingfactorAIP1:actin-interactingprotein1ARP:actin-relatedproteinARPC:actin-relatedprotein2/3complexCAP1andCAP2:cyclase-associatedprotein1and2CARMIL:cappingprotein,Arp2/3,andmyosinlinkerDAAM:dishevelled-associatedactivatorofmorphogenesisEna:EnabledEPLIN:epi
18、thelialproteinlostinneoplasmEps8:EGFreceptorpathwaysubstrate8EVL:Ena/VASP-likeproteinFHOD:forminhomology-2domain-containingproteinFMN:forminFRL:formin-relatedgeneinleukocyteshDia:humanhomologofDrosophilaDiaphanousINF:invertedforminLmod:leiomodinMena:mammalianenabledMIM:missinginmetastasisN-WASP:neuronalWiskott-AldrichSyndromeproteinSCAR/WAVE:suppressorofcAMPreceptor/WASPfamilyverprolin-homologousproteinTmod:tropomodulinVASP:vasodilator-stimulatedphosphoproteinWASP:Wiskott-AldrichSyndromeproteinWIP:WASP-interactingproteinWIRE/WICH:WIP-related/WIPandCR16homologousprotein