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Snapshot: Actin Regulators I Anosha D 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 Biochemical Function H. sapiens D. melanogaster C. elegans A. thaliana S. cerevisiae Actin Nucleators Formins associates with barbed ends, *hDia1, 2, 3, FHOD1, Diaphanous/Dia, Dia/CYK-1, DAAM, AtFH1-4, 5, 6-21 Bni1, Bnr1 promotes nucleation 2, 3, 4, DAAM1, 2, Cappucino/FMN, FRL, FHOD, INF FMN1, 2, FRL1, 2, 3, DAAM, FRL, FHOD, INF1, 2, Delphilin INF Spir nucleates unbranched fi laments Spir-1, Spir-2 Spir/spire Arp2/3 complex polymerizes Y-branched fi lament ARP2, ARP3, ARP2, ARP3, ARPC1, ARX1-7 ARP2, ARP3, ARPC1-5 Arp2, Arp3, Arc40, networks ARPC1A, 1B, 2, 3, 2, 3A, 3B, 4, 5, 5L 35, 18, 19, 15 4, 5, 5L CARMIL links capping protein, Arp2/3 and CARMIL DCarmil †Q21301 myosin I Coronin binds F-actin and Arp2/3 complex, coronin 1A, B, C; Coro/Coronin, Dpod1 COR-1, POD-1 Crn1 enhances actin depolymerization 2A, B; 7 Cortactin activates/modulates Arp2/3 complex, cortactin, HS1 DCortactin binds F-actin SCAR/WAVE activates Arp2/3 complex SCAR1, SCAR2, SCAR WVE-1 AtSCAR 1, 2, 3, 4 family SCAR3 Arp2/3 complex regulators WASP family activates Arp2/3 complex *WASP, N-WASP WASp WSP-1 Las17/Bee1 G-Actin Binding Proteins CAP/Srv2 recycles actin monomers CAP1, CAP2 Act up/Capulet CAS-1 AtCAP1 Srv2 Profi lin promotes actin monomer addition at profi lin 1, 2, 3, 4 Chickadee PFN1, 2, 3 PRF1-3 (vegetative), Pfy1 barbed ends PRF4-5 (reproductive) Thymosin β4 sequesters G-actin thymosin β4 Ciboulot TTH-1 Verprolin/WIP binds actin monomers, WASP WIP, WIRE/WICH, †Q8MLU0 WIP-1 Vrp1 CR16 F-Actin Binding Proteins Identifi ed Cellular Role: X Membrane traffi cking and phagocytosis Ena/VASP family antagonizes CapZ capping at fi lament Mena, VASP, EVL Enabled UNC-34 X Cytokinesis ends, recruits profi lin X Cell surface organization and dynamics MIM binds both G- and F-actin, may MIM X Cell adhesion regulate nucleation-promoting factors X Multiple functions Pointed End Capping Proteins X Other/unknown Tropomodulin/ caps pointed ends, binds tropomyosin Tmod1, 2, 3, 4, Sanpodo TMD-1, TMD-2 †UNIPROT database accession number Tmod Lmod1, 2, 3 *Mutation linked to human disease Barbed End Capping Proteins AIP1 promotes depolymerization by ADF/ AIP1/WDR1 Aip1 AIP-1/UNC-78 AtAIP1 Aip1 cofi lin CapG caps barbed ends (calcium- capG CapG dependent) CapZ/capping heterodimer caps barbed ends capZ (A1-3, B1-2) CapZ (cpa, cpb) CAP-1, CAP-2 AtCPA, AtCPB Cap1, Cap2 protein/β-actinin Eps8 caps barbed ends, involved in Rac Eps8, Eps8L1, 2, 3 Arouser, †Q95TJ6 EPS-8 signalling Actin Depolymerizing/Severing Proteins ADF/cofi lin promotes actin fi lament disassembly cofi lin1, cofi lin2, ADF Cofi lin/Twinstar UNC-60A, B AtADF1-12 Cof1 Gelsolin/villin severs actin fi laments gelsolin, adseverin/ Gelsolin, Villin-like/ gelsolin (†Q21253), VLN1-5 superfamily scinderin, villin, Quail, Flightless I supervillin advillin, supervillin, (†P91041), FLI-1 fl ightless I Twinfi lin inhibits actin nucleotide exchange, twinfi lin-1/A6, Twinfi lin †U46668 Twf1 severs actin twinfi lin-2 Actin Bundling/Crosslinking Proteins α-actinin connects and organizes actin fi laments α-actinin1-4 α-actinin/Flightless A ATN-1 EPLIN stabilizes and bundles actin fi laments EPLIN Espin forms parallel actin bundles *espin Forked Fascin bundles actin fi laments fascin 1, 2, 3 Singed Filamin orthogonally crosslinks actin fi laments fi lamin *A, *B, C Jitterbug, Cheerio †Q18109 Fimbrin/plastin bundles actin fi laments plastin 1-3 (I, L, T) Fimbrin †Q965Y6 AtFIM1 Sac6 See online version for references and abbreviations. Actin Regulators II will appear in the March 9 issue of Cell. 626 Cell 128, February 9, 2007 ©2007 Elsevier Inc. DOI 10.1016/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). The verprolin family of proteins: Regulators of cell morphogenesis and endocytosis. FEBS Lett. 579, 5253–5259. Daly, R.J. (2004). Cortactin signalling and dynamic actin networks. Biochem. J. 382, 13–25. dos Remedios, C.G., Chhabra, D., Kekic, M., Dedova, I.V., Tsubakihara, M., Berry, D.A., and Nosworthy, N.J. (2003). Actin binding proteins: regulation of cytoskeletal microfilaments. Physiol. Rev. 83, 433–473. Goley, E.D., and Welch, M.D. (2006). The ARP2/3 complex: An actin nucleator comes of age. Nat. Rev. Mol. Cell Biol. 7, 713–726. Higgs, H.N., and Peterson, K.J. (2005). Phylogenetic analysis of the formin homology 2 domain. Mol. Biol. Cell 16, 1–13. Kerkhoff, E. (2006). Cellular functions of the Spir actin-nucleation factors. Trends Cell Biol. 16, 477–483. Krause, M., Dent, E.W., Bear, J.E., Loureiro, J.J., and Gertler, F.B. (2003). Ena/VASP proteins: Regulators of the actin cytoskeleton and cell migration. Annu. Rev. Cell Dev. Biol. 19, 541–564. Paavilainen, V.O., Bertling, E., Falck, S., and Lappalainen, P. (2004). Regulation of cytoskeletal dynamics by actin-monomer-binding proteins. Trends Cell Biol. 14, 386–394. Silacci, P., Mazzolai, L., Gauci, C., Stergiopulos, N., Yin, H.L., and Hayoz, D. (2004). Gelsolin superfamily proteins: Key regulators of cellular functions. Cell. Mol. Life Sci. 61, 2614–2623. Uetrecht, A.C., and Bear, J.E. (2006). Coronins: The return of the crown. Trends Cell Biol. 16, 421–426. ABBREVIATIONS ADF: actin-depolymerizing factor AIP1: actin-interacting protein 1 ARP: actin-related protein ARPC: actin-related protein 2/3 complex CAP1 and CAP2: cyclase-associated protein 1 and 2 CARMIL: capping protein, Arp2/3, and myosin linker DAAM: dishevelled-associated activator of morphogenesis Ena: Enabled EPLIN: epithelial protein lost in neoplasm Eps8: EGF receptor pathway substrate 8 EVL: Ena/VASP-like protein FHOD: formin homology-2 domain-containing protein FMN: formin FRL: formin-related gene in leukocytes hDia: human homolog of Drosophila Diaphanous INF: inverted formin Lmod: leiomodin Mena: mammalian enabled MIM: missing in metastasis N-WASP: neuronal Wiskott-Aldrich Syndrome protein SCAR/WAVE: suppressor of cAMP receptor/WASP family verprolin-homologous protein Tmod: tropomodulin VASP: vasodilator-stimulated phosphoprotein WASP: Wiskott-Aldrich Syndrome protein WIP: WASP-interacting protein WIRE/WICH: WIP-related/WIP and CR16 homologous protein 626.e1 Cell 128, February 9, 2007 ©2007 Elsevier Inc. DOI 10.1016/j.cell.2007.02.001.
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