SnapShot: Actin Regulators I

Anosha D. Siripala and Matthew D. Welch Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA
Representative Proteins Protein Family Actin Nucleators
Formins associateswithbarbedends, promotesnucleation *hDia1,2,3,FHOD1, 2,3,4,DAAM1,2, FMN1,2,FRL1,2,3, INF1,2,Delphilin Spir-1,Spir-2 ARP2,ARP3, ARPC1A,1B,2,3, 4,5,5L CARMIL coronin1A,B,C; 2A,B;7 cortactin,HS1 SCAR1,SCAR2, SCAR3 *WASP,N-WASP Diaphanous/Dia, Cappucino/FMN, DAAM,FRL,FHOD, INF Spir/spire ARP2,ARP3,ARPC1, 2,3A,3B,4,5,5L DCarmil Coro/Coronin,Dpod1 DCortactin SCAR WASp WVE-1 WSP-1 AtSCAR1,2,3,4 Las17/Bee1 ARX1-7 ARP2,ARP3,ARPC1-5 Arp2,Arp3,Arc40, 35,18,19,15 Dia/CYK-1,DAAM, FRL,FHOD,INF AtFH1-4,5,6-21 Bni1,Bnr1

Biochemical Function

H. sapiens

D. melanogaster

C. elegans

A. thaliana

S. cerevisiae

Spir Arp2/3 complex

nucleatesunbranchedfilaments polymerizesY-branchedfilament networks linkscappingprotein,Arp2/3and myosinI bindsF-actinandArp2/3complex, enhancesactindepolymerization activates/modulatesArp2/3complex, bindsF-actin activatesArp2/3complex activatesArp2/3complex

Arp2/3 complex regulators

CARMIL Coronin Cortactin SCAR/WAVE family WASP family

Q21301 Crn1

COR-1,POD-1

G-Actin Binding Proteins

CAP/Srv2 Prolin Thymosin 4 Verprolin/WIP recyclesactinmonomers promotesactinmonomeradditionat barbedends sequestersG-actin bindsactinmonomers,WASP CAP1,CAP2 profilin1,2,3,4 thymosin4 WIP,WIRE/WICH, CR16 Actup/Capulet Chickadee Ciboulot

CAS-1 PFN1,2,3 TTH-1 WIP-1

AtCAP1 PRF1-3(vegetative), PRF4-5(reproductive)

Srv2 Pfy1

Q8MLU0

Vrp1

F-Actin Binding Proteins

Ena/VASP family MIM antagonizesCapZcappingatfilament ends,recruitsprofilin bindsbothG-andF-actin,may regulatenucleation-promotingfactors Mena,VASP,EVL MIM Enabled UNC-34

Pointed End Capping Proteins

Tropomodulin/ Tmod capspointedends,bindstropomyosin Tmod1,2,3,4, Lmod1,2,3 Sanpodo TMD-1,TMD-2

Identied Cellular Role: XMembranetraffickingandphagocytosis XCytokinesis XCellsurfaceorganizationanddynamics XCelladhesion XMultiplefunctions XOther/unknown UNIPROTdatabaseaccessionnumber *Mutationlinkedtohumandisease

Barbed End Capping Proteins

AIP1 CapG CapZ/capping protein/-actinin Eps8 promotesdepolymerizationbyADF/ cofilin capsbarbedends(calciumdependent) heterodimercapsbarbedends capsbarbedends,involvedinRac signalling AIP1/WDR1 capG capZ(A1-3,B1-2) Eps8,Eps8L1,2,3 Aip1 CapG CapZ(cpa,cpb) Arouser,Q95TJ6 CAP-1,CAP-2 EPS-8 AtCPA,AtCPB Cap1,Cap2 AIP-1/UNC-78 AtAIP1 Aip1

Actin Depolymerizing/Severing Proteins

ADF/colin Gelsolin/villin superfamily promotesactinfilamentdisassembly seversactinfilaments cofilin1,cofilin2,ADF gelsolin,adseverin/ scinderin,villin, advillin,supervillin, ightlessI twinfilin-1/A6, twinfilin-2 Cofilin/Twinstar Gelsolin,Villin-like/ Quail,FlightlessI UNC-60A,B gelsolin(Q21253), supervillin (P91041),FLI-1

AtADF1-12 VLN1-5

Cof1

Twinlin

inhibitsactinnucleotideexchange, seversactin

Twinfilin

U46668

Twf1

Actin Bundling/Crosslinking Proteins

-actinin EPLIN Espin Fascin Filamin Fimbrin/plastin connectsandorganizesactinfilaments stabilizesandbundlesactinfilaments formsparallelactinbundles bundlesactinfilaments orthogonallycrosslinksactinfilaments bundlesactinfilaments -actinin1-4 EPLIN *espin fascin1,2,3 filamin*A,*B,C plastin1-3(I,L,T) Forked Singed Jitterbug,Cheerio Fimbrin

-actinin/FlightlessA

ATN-1

Q18109 Q965Y6 AtFIM1 Sac6

Seeonlineversionforreferencesandabbreviations. ActinRegulatorsIIwillappearintheMarch9issueofCell.

626 Cell128,February9,20072007ElsevierInc. DOI10.1016/j.cell.2007.02.001

SnapShot: Actin Regulators I

Anosha D. Siripala and Matthew D. Welch Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA

RefeRences Aspenstrom,P.(2005).Theverprolinfamilyofproteins: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:regulationofcytoskeletal microfilaments.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-nucleationfactors.TrendsCellBiol.16,477483. Krause,M.,Dent,E.W.,Bear,J.E.,Loureiro,J.J.,andGertler,F.B.(2003).Ena/VASPproteins:Regulatorsoftheactincytoskeletonandcellmigration.Annu.Rev.Cell Dev.Biol.19,541564. Paavilainen,V.O.,Bertling,E.,Falck,S.,andLappalainen,P.(2004).Regulationofcytoskeletaldynamicsbyactin-monomer-bindingproteins.TrendsCellBiol.14, 386394. Silacci,P.,Mazzolai,L.,Gauci,C.,Stergiopulos,N.,Yin,H.L.,andHayoz,D.(2004).Gelsolinsuperfamilyproteins:Keyregulatorsofcellularfunctions.Cell.Mol.Life Sci.61,26142623. Uetrecht,A.C.,andBear,J.E.(2006).Coronins:Thereturnofthecrown.TrendsCellBiol.16,421426.

AbbReviAtions ADF:actin-depolymerizingfactor AIP1:actin-interactingprotein1 ARP:actin-relatedprotein ARPC:actin-relatedprotein2/3complex CAP1andCAP2:cyclase-associatedprotein1and2 CARMIL:cappingprotein,Arp2/3,andmyosinlinker DAAM:dishevelled-associatedactivatorofmorphogenesis Ena:Enabled EPLIN:epithelialproteinlostinneoplasm Eps8:EGFreceptorpathwaysubstrate8 EVL:Ena/VASP-likeprotein FHOD:forminhomology-2domain-containingprotein FMN:formin FRL:formin-relatedgeneinleukocytes hDia:humanhomologofDrosophilaDiaphanous INF:invertedformin Lmod:leiomodin Mena:mammalianenabled MIM:missinginmetastasis N-WASP:neuronalWiskott-AldrichSyndromeprotein SCAR/WAVE:suppressorofcAMPreceptor/WASPfamilyverprolin-homologousprotein Tmod:tropomodulin VASP:vasodilator-stimulatedphosphoprotein WASP:Wiskott-AldrichSyndromeprotein WIP:WASP-interactingprotein WIRE/WICH:WIP-related/WIPandCR16homologousprotein

626.e1 Cell128,February9,20072007ElsevierInc. DOI10.1016/j.cell.2007.02.001

SnapShot: Actin Regulators II

Anosha D. Siripala and Matthew D. Welch Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA
Representative Proteins Protein Family Endocytosis and Exocytosis
ABP1/drebrin EPS15 HIP1R Synapsin mABP1,drebrin,drebrinlike EPS15 HIP1R synapsinIa,Ib,IIa,IIb,III

H. sapiens

D. melanogaster

C. elegans

A. thaliana

S. cerevisiae

Q95RN0

Q9XUT0

Abp1 Q56WL2 Pan1 Sla2

Eps-15

EHS-1

Q8MQK1

O62142

Synapsin

SNN-1

Plasma Membrane Association

Anillin Annexins ERM proteins MARCKS Merlin Protein 4.1 Spectrin anillin annexinA111,13(actin binding:1,2,6) ezrin,radixin,moesin MARCKS,MRP/ MACMARCKS/F52 *merlin/NF2 4.1R,G,N,B -spectrin(12),-spectrin (14), heavy-spectrin/ karst Scraps AnnexinB9-11 DMoesin Akap200 Merlin Coracle -spectrin,-spectrin, heavyspectrin/Karst SPC-1(-spectrin),UNC-70 (-spectrin),SMA-1( heavyspectrin) NFM-1 ANI-1,2,3 NEX-14 ERM-1 ANN1-8

Cell-Cell Junctions
-catenin Afadin ZO-1 -catenin13 afadin/AF6 ZO-1,ZO-2,ZO-3 -catenin Canoe ZO-1/Polychaetoid HMP-1 AFD-1

Q56VX4

Identied Cellular Role: XMembranetraffickingandphagocytosis XCytokinesis XCellsurfaceorganizationanddynamics XCelladhesion XMultiplefunctions XOther/unknown UNIPROTdatabaseaccessionnumber *Mutationlinkedtohumandisease

Cell-Extracellular Matrix Junctions

Dystrophin/utrophin LASP Palladin Parvin Plakins Talin Tensin Vinculin Zyxin/paxillin *dystrophin,utrophin/ DRP1,DRP2 LASP-1,LASP-2,LIMnebulette palladin -, -, -parvin BPAG1,MACF1,plectin talin12 tensin13 vinculin zyxin,paxillin

Dystrophin Lasp

DYS-1

P34416

Q9VWD0

PAT-6(-parvin) VAB-10

Shortstop/Kakapo Rhea/Tendrils Blistery/Tensin Vinculin Zyx102,Dpax

Q8S8J6,Q38843, Q9C7V7

Q22860 P92160

DEB-1 ZYX-1,paxillin(Q09476)

Motor Proteins and Regulators

Caldesmon Calponin Myosin family Tropomyosin Troponin caldesmon calponin13 Myosintypes1,2,3,*5,*6, *7,9,10,*15,16,18,19 tropomyosin1,*2,*3,4 troponinT*1,*2,3;C1,2; I1,2,*3 Crtp Chd64 Myosintypes1,2,3,5,6,7, 15,18,20 Tm1,Tm2 TroponinT/Upheld,Troponin I/Wingsup,TroponinC1-3, Tina-1 CPN-14 Myosintypes1,2,5,6,7,9,12 LEV-11/TMY-1 TNI-1-4,TNC-1-2,TNT-1-4 Myosintypes8,11

Scp1 Myosintypes1,2,5 Tpm1,Tpm2

Q8LE98

Muscle Components
Myopalladin Nebulin Titin/connectin myopalladin,*myotilin *nebulin,*nebulette,N-RAP *titin/connectin Nebulin D-titin,Projectin/Twitchin

P34416

Ce-titin,stretchin

Nuclear Actin-Associated Proteins

Chromatin-remodeling complexes hnRNP proteins Nuclear DNA Helicase II BAF,PBAF,TIP60,p400 DBP40(R. norvegicus) NDHII BAP hrp36,hrp65(C. tentans) Maleless/MLE RHA-1 Ino80,NuA4

Seeonlineversionforreferencesandabbreviations. ActinRegulatorsIappearedintheFebruary9issueofCell.

1014 Cell128,March9,20072007ElsevierInc. DOI10.1016/j.cell.2007.02.021

SnapShot: Actin Regulators II

Anosha D. Siripala and Matthew D. Welch Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA

RefeRences Berg,J.S.,Powell,B.C.,andCheney,R.E.(2001).Amillennialmyosincensus.Mol.Biol.Cell12,780794. Bettinger,B.T.,Gilbert,D.M.,andAmberg,D.C.(2004).Actinupinthenucleus.Nat.Rev.Mol.CellBiol.5,410415. Bretscher,A.,Edwards,K.,andFehon,R.G.(2002).ERMproteinsandmerlin:Integratorsatthecellcortex.Nat.Rev.Mol.CellBiol.3,586599. Calderwood,D.A.,Shattil,S.J.,andGinsberg,M.H.(2000).Integrinsandactinfilaments:Reciprocalregulationofcelladhesionandsignaling.J.Biol.Chem.275, 2260722610. Clark,K.A.,McElhinny,A.S.,Beckerle,M.C.,andGregorio,C.C.(2002).Striatedmusclecytoarchitecture:Anintricatewebofformandfunction.Annu.Rev.CellDev. Biol.18,637706. Critchley,D.R.(2004).Cytoskeletalproteinstalinandvinculininintegrin-mediatedadhesion.Biochem.Soc.Trans.32,831836. Goodson,H.V.,andDawson,S.C.(2006).Multiplyingmyosins.Proc.Natl.Acad.Sci.USA103,34983499. Hayes,M.J.,Rescher,U.,Gerke,V.,andMoss,S.E.(2004).Annexin-actininteractions.Traffic5,571576. Kaksonen,M.,Toret,C.P.,andDrubin,D.G.(2006).Harnessingactindynamicsforclathrin-mediatedendocytosis.Nat.Rev.Mol.CellBiol.7,404414. Lo,S.H.(2006).Focaladhesions:Whatsnewinside.Dev.Biol.294,280291.

AbbReviAtions ABP1:actin-bindingprotein1 Akap200:Akinaseanchorprotein200 BAF:BRG1-associatedfactor BAP:Brahma-associatedprotein BIN2:bridgingintegrator2 BPAG1:bullouspemphigoidantigen1 Crtp:caldesmon-relatedprotein DBP40:DNA-bindingprotein40 DRP1:dystrophin-relatedprotein1 DRP2:dystrophin-relatedprotein2 EPS15:epidermalgrowthfactorreceptorpathwaysubstrate15 HIP1R:huntingtin-interactingprotein1related hrp:heterogeneousnuclearribonucleoprotein LASP:LimandSH3protein MACF1:microtubule-actincrosslinkingfactor1 MARCKS:myristoylatedalanine-richproteinkinaseCsubstrate MRP/MACMARCKS:MARCKS-relatedprotein/macrophageMARCKS NDHII:nuclearDNAhelicaseII N-RAP:nebulin-relatedanchoringprotein NF2:neurofibromin2 NuA4:nucleosomeacetyltransferaseofH4 PBAF:polybromo-associatedBRG1associatedfactor TIP60:HIV-1Tat-interactingproteinof60kilodaltons ZO:zonulaoccludens

1014.e1 Cell128,March9,20072007ElsevierInc. DOI10.1016/j.cell.2007.02.021