Formin' cellular structures: Physiological roles of Diaphanous (Dia) in actin dynamics

Communicative and Integrative Biology

Volumn 6, Issue 6, 2013, Pages

  Bogdan, Sven ^a   Schultz, Jörg ^b   Grosshans, Jörg ^c  

^a UNIVERSITY OF MÜNSTER   (Germany)

^b UNIVERSITY OF WÜRZBURG   (Germany)

^c UNIVERSITY OF GÖTTINGEN   (Germany)

Author keywords

Actin; Cytoskeleton; Development; Drosophila; Formin; Nucleator

Indexed keywords

EID: 84894100330     PISSN: 19420889     EISSN: 19420889     Source Type: Journal    
DOI: 10.4161/cib.27634     Document Type: Review

References (174)

1. Castrillon DH, Wasserman SA. Diaphanous is required for cytokinesis in Drosophila and shares domains of similarity with the products of the limb deformity gene. Development 1994; 120:3367-77; PMID:7821209.
2. Campellone KG, Welch MD. A nucleator arms race: cellular control of actin assembly. Nat Rev Mol Cell Biol 2010; 11:237-51; PMID:20237478; http://dx.doi.org/10.1038/nrm2867.
3. Higgs HN, Peterson KJ. Phylogenetic analysis of the formin homology 2 domain. Mol Biol Cell 2005; 16:1-13; PMID:15509653; http://dx.doi. org/10.1091/mbc.E04-07-0565.
4. Schönichen A, Geyer M. Fifteen formins for an actin filament: a molecular view on the regulation of human formins. Biochim Biophys Acta 2010; 1803:152-63; PMID:20102729; http://dx.doi. org/10.1016/j.bbamcr.2010.01.014.
5. Higgs HN. Formin proteins: a domain-based approach. Trends Biochem Sci 2005; 30:342-53; PMID:15950879; http://dx.doi.org/10.1016/j. tibs.2005.04.014.
6. Rivero F, Muramoto T, Meyer AK, Urushihara H, Uyeda TQ, Kitayama C. A comparative sequence analysis reveals a common GBD/FH3-FH1-FH2-DAD architecture in formins from Dictyostelium, fungi and metazoa. BMC Genomics 2005; 6:28; PMID:15740615; http://dx.doi. org/10.1186/1471-2164-6-28.
7. Chalkia D, Nikolaidis N, Makalowski W, Klein J, Nei M. Origins and evolution of the formin multigene family that is involved in the formation of actin filaments. Mol Biol Evol 2008; 25:2717-33; PMID:18840602; http://dx.doi.org/10.1093/molbev/msn215.
8. Grunt M, Zárskỳ V, Cvrcková F. Roots of angiosperm formins: the evolutionary history of plant FH2 domain-containing proteins. BMC Evol Biol 2008; 8:115; PMID:18430232; http://dx.doi. org/10.1186/1471-2148-8-115.
9. Letunic I, Doerks T, Bork P. SMART 7: recent updates to the protein domain annotation resource. Nucleic Acids Res 2012; 40:D302-5; PMID:22053084; http://dx.doi.org/10.1093/nar/gkr931.
10. Edgar RC. MUSCLE: a multiple sequence alignment method with reduced time and space complexity. BMC Bioinformatics 2004; 5:113; PMID:15318951; http://dx.doi.org/10.1186/1471-2105-5-113.
11. Darriba D, Taboada GL, Doallo R, Posada D. ProtTest 3: fast selection of best-fit models of protein evolution. Bioinformatics 2011; 27:1164-5; PMID:21335321; http://dx.doi.org/10.1093/bioinformatics/btr088.
12. Lynch M, Conery JS. The evolutionary fate and consequences of duplicate genes. Science 2000; 290:1151-5; PMID:11073452; http://dx.doi.org/10.1126/science.290.5494.1151.
13. Lammers M, Meyer S, Kühlmann D, Wittinghofer A. Specificity of interactions between mDia isoforms and Rho proteins. J Biol Chem 2008; 283:35236-46; PMID:18829452; http://dx.doi.org/10.1074/jbc. M805634200.
14. Gu X. Maximum-likelihood approach for gene family evolution under functional divergence. Mol Biol Evol 2001; 18:453-64; PMID:11264396; http://dx.doi. org/10.1093/oxfordjournals.molbev.a003824.
15. Mazin PV, Gelfand MS, Mironov AA, Rakhmaninova AB, Rubinov AR, Russell RB, Kalinina OV. An automated stochastic approach to the identification of the protein specificity determinants and functional subfamilies. Algorithms Mol Biol 2010; 5:29; PMID:20633297; http://dx.doi. org/10.1186/1748-7188-5-29.
16. Otomo T, Otomo C, Tomchick DR, Machius M, Rosen MK. Structural basis of Rho GTPasemediated activation of the formin mDia1. Mol Cell 2005; 18:273-81; PMID:15866170; http://dx.doi. org/10.1016/j.molcel.2005.04.002.
17. Kursula P, Kursula I, Massimi M, Song YH, Downer J, Stanley WA, Witke W, Wilmanns M. Highresolution structural analysis of mammalian profilin 2a complex formation with two physiological ligands: the formin homology 1 domain of mDia1 and the proline-rich domain of VASP. J Mol Biol 2008; 375:270-90; PMID:18001770; http://dx.doi. org/10.1016/j.jmb.2007.10.050.
18. Chang F, Drubin D, Nurse P. cdc12p, a protein required for cytokinesis in fission yeast, is a component of the cell division ring and interacts with profilin. J Cell Biol 1997; 137:169-82; PMID:9105045; http://dx.doi.org/10.1083/jcb.137.1.169.
19. Watanabe N, Madaule P, Reid T, Ishizaki T, Watanabe G, Kakizuka A, Saito Y, Nakao K, Jockusch BM, Narumiya S. p140mDia, a mammalian homolog of Drosophila diaphanous, is a target protein for Rho small GTPase and is a ligand for profilin. EMBO J 1997; 16:3044-56; PMID:9214622; http://dx.doi.org/10.1093/emboj/16.11.3044.
20. Romero S, Le Clainche C, Didry D, Egile C, Pantaloni D, Carlier MF. Formin is a processive motor that requires profilin to accelerate actin assembly and associated ATP hydrolysis. Cell 2004; 119:419-29; PMID:15507212; http://dx.doi. org/10.1016/j.cell.2004.09.039.
21. Kovar DR, Pollard TD. Progressing actin: Formin as a processive elongation machine. Nat Cell Biol 2004; 6:1158-9; PMID:15573095; http://dx.doi. org/10.1038/ncb1204-1158.
22. Yan S, Lv Z, Winterhoff M, Wenzl C, Zobel T, Faix J, Bogdan S, Grosshans J. The F-BAR protein Cip4/Toca-1 antagonizes the formin Diaphanous in membrane stabilization and compartmentalization. J Cell Sci 2013; 126:1796-805; PMID:23424199; http://dx.doi.org/10.1242/jcs.118422.
23. Satoh S, Tominaga T. mDia-interacting protein acts downstream of Rho-mDia and modifies Src activation and stress fiber formation. J Biol Chem 2001; 276:39290-4; PMID:11509578; http://dx.doi. org/10.1074/jbc.M107026200.
24. Fujiwara T, Mammoto A, Kim Y, Takai Y. Rho small G-protein-dependent binding of mDia to an Src homology 3 domain-containing IRSp53/BAIAP2. Biochem Biophys Res Commun 2000; 271:626-9; PMID:10814512; http://dx.doi.org/10.1006/bbrc.2000.2671.
25. Eisenmann KM, Harris ES, Kitchen SM, Holman HA, Higgs HN, Alberts AS. Dia-interacting protein modulates formin-mediated actin assembly at the cell cortex. Curr Biol 2007; 17:579-91; PMID:17398099; http://dx.doi.org/10.1016/j. cub.2007.03.024.
26. Esue O, Harris ES, Higgs HN, Wirtz D. The filamentous actin cross-linking/bundling activity of mammalian formins. J Mol Biol 2008; 384:324-34; PMID:18835565; http://dx.doi.org/10.1016/j. jmb.2008.09.043.
27. Harris ES, Rouiller I, Hanein D, Higgs HN. Mechanistic differences in actin bundling activity of two mammalian formins, FRL1 and mDia2. J Biol Chem 2006; 281:14383-92; PMID:16556604; http://dx.doi.org/10.1074/jbc.M510923200.
28. Hudson BI, Kalea AZ, Del Mar Arriero M, Harja E, Boulanger E, D'Agati V, Schmidt AM. Interaction of the RAGE cytoplasmic domain with diaphanous-1 is required for ligand-stimulated cellular migration through activation of Rac1 and Cdc42. J Biol Chem 2008; 283:34457-68; PMID:18922799; http://dx.doi.org/10.1074/jbc.M801465200.
29. Kupi T, Gróf P, Nyitrai M, Belágyi J. Interaction of formin FH2 with skeletal muscle actin. EPR and DSC studies. Eur Biophys J 2013; 42:757-65; PMID:23949957; http://dx.doi.org/10.1007/s00249-013-0922-0.
30. Copeland JW, Copeland SJ, Treisman R. Homooligomerization is essential for F-actin assembly by the formin family FH2 domain. J Biol Chem 2004; 279:50250-6; PMID:15371418; http://dx.doi. org/10.1074/jbc.M404429200.
31. Shimada A, Nyitrai M, Vetter IR, Kühlmann D, Bugyi B, Narumiya S, Geeves MA, Wittinghofer A. The core FH2 domain of diaphanous-related formins is an elongated actin binding protein that inhibits polymerization. Mol Cell 2004; 13:511-22; PMID:14992721; http://dx.doi.org/10.1016/S1097-2765(04)00059-0.
32. Kovar DR, Pollard TD. Insertional assembly of actin filament barbed ends in association with formins produces piconewton forces. Proc Natl Acad Sci U S A 2004; 101:14725-30; PMID:15377785; http://dx.doi. org/10.1073/pnas.0405902101.
33. Mizuno H, Higashida C, Yuan Y, Ishizaki T, Narumiya S, Watanabe N. Rotational movement of the formin mDia1 along the double helical strand of an actin filament. Science 2011; 331:80-3; PMID:21148346; http://dx.doi.org/10.1126/science.1197692.
34. Homem CC, Peifer M. Exploring the roles of diaphanous and enabled activity in shaping the balance between filopodia and lamellipodia. Mol Biol Cell 2009; 20:5138-55; PMID:19846663; http://dx.doi. org/10.1091/mbc.E09-02-0144.
35. Lewkowicz E, Herit F, Le Clainche C, Bourdoncle P, Perez F, Niedergang F. The microtubule-binding protein CLIP-170 coordinates mDia1 and actin reorganization during CR3-mediated phagocytosis. J Cell Biol 2008; 183:1287-98; PMID:19114595; http://dx.doi. org/10.1083/jcb.200807023.
36. Schirenbeck A, Arasada R, Bretschneider T, Stradal TE, Schleicher M, Faix J. The bundling activity of vasodilator-stimulated phosphoprotein is required for filopodium formation. Proc Natl Acad Sci U S A 2006; 103:7694-9; PMID:16675552; http://dx.doi. org/10.1073/pnas.0511243103.
37. Grosse R, Copeland JW, Newsome TP, Way M, Treisman R. A role for VASP in RhoA-Diaphanous signalling to actin dynamics and SRF activity. EMBO J 2003; 22:3050-61; PMID:12805219; http://dx.doi. org/10.1093/emboj/cdg287.
38. Lammers M, Rose R, Scrima A, Wittinghofer A. The regulation of mDia1 by autoinhibition and its release by Rho*GTP. EMBO J 2005; 24:4176-87; PMID:16292343; http://dx.doi.org/10.1038/sj.emboj.7600879.
39. Li F, Higgs HN. The mouse Formin mDia1 is a potent actin nucleation factor regulated by autoinhibition. Curr Biol 2003; 13:1335-40; PMID:12906795; http://dx.doi.org/10.1016/S0960-9822(03)00540-2.
40. Li F, Higgs HN. Dissecting requirements for autoinhibition of actin nucleation by the formin, mDia1. J Biol Chem 2005; 280:6986-92; PMID:15591319; http://dx.doi.org/10.1074/jbc.M411605200.
41. Rose R, Weyand M, Lammers M, Ishizaki T, Ahmadian MR, Wittinghofer A. Structural and mechanistic insights into the interaction between Rho and mammalian Dia. Nature 2005; 435:513-8; PMID:15864301; http://dx.doi.org/10.1038/nature03604.
42. Sakamoto S, Ishizaki T, Okawa K, Watanabe S, Arakawa T, Watanabe N, Narumiya S. Liprin-α controls stress fiber formation by binding to mDia and regulating its membrane localization. J Cell Sci 2012; 125:108-20; PMID:22266902; http://dx.doi. org/10.1242/jcs.087411.
43. Watanabe S, Okawa K, Miki T, Sakamoto S, Morinaga T, Segawa K, Arakawa T, Kinoshita M, Ishizaki T, Narumiya S. Rho and anillin-dependent control of mDia2 localization and function in cytokinesis. Mol Biol Cell 2010; 21:3193-204; PMID:20660154; http://dx.doi.org/10.1091/mbc.E10-04-0324.
44. Ryu JR, Echarri A, Li R, Pendergast AM. Regulation of cell-cell adhesion by Abi/Diaphanous complexes. Mol Cell Biol 2009; 29:1735-48; PMID:19158278; http://dx.doi.org/10.1128/MCB.01483-08.
45. Schwaibold EM, Brandt DT. Identification of Neurochondrin as a new interaction partner of the FH3 domain of the Diaphanous-related formin Dia1. Biochem Biophys Res Commun 2008; 373:366-72; PMID:18572016; http://dx.doi.org/10.1016/j. bbrc.2008.06.042.
46. Brandt DT, Marion S, Griffiths G, Watanabe T, Kaibuchi K, Grosse R. Dia1 and IQGAP1 interact in cell migration and phagocytic cup formation. J Cell Biol 2007; 178:193-200; PMID:17620407; http://dx.doi.org/10.1083/jcb.200612071.
47. Rousso T, Shewan AM, Mostov KE, Schejter ED, Shilo BZ. Apical targeting of the formin Diaphanous in Drosophila tubular epithelia. Elife 2013; 2:e00666; PMID:23853710; http://dx.doi.org/10.7554/eLife.00666.
48. Gorelik R, Yang C, Kameswaran V, Dominguez R, Svitkina T. Mechanisms of plasma membrane targeting of formin mDia2 through its amino terminal domains. Mol Biol Cell 2011; 22:189-201; PMID:21119010; http://dx.doi.org/10.1091/mbc.E10-03-0256.
49. Ramalingam N, Zhao H, Breitsprecher D, Lappalainen P, Faix J, Schleicher M. Phospholipids regulate localization and activity of mDia1 formin. Eur J Cell Biol 2010; 89:723-32; PMID:20619927; http://dx.doi. org/10.1016/j.ejcb.2010.06.001.
50. Maiti S, Michelot A, Gould C, Blanchoin L, Sokolova O, Goode BL. Structure and activity of full-length formin mDia1. Cytoskeleton (Hoboken) 2012; 69:393-405; PMID:22605659; http://dx.doi.org/10.1002/cm.21033.
51. Jaiswal R, Stepanik V, Rankova A, Molinar O, Goode BL, McCartney BM. Drosophila homologues of adenomatous polyposis coli (APC) and the formin diaphanous collaborate by a conserved mechanism to stimulate actin filament assembly. J Biol Chem 2013; 288:13897-905; PMID:23558679; http://dx.doi. org/10.1074/jbc.M113.462051.
52. Breitsprecher D, Jaiswal R, Bombardier JP, Gould CJ, Gelles J, Goode BL. Rocket launcher mechanism of collaborative actin assembly defined by single-molecule imaging. Science 2012; 336:1164-8; PMID:22654058; http://dx.doi.org/10.1126/science.1218062.
53. Okada K, Bartolini F, Deaconescu AM, Moseley JB, Dogic Z, Grigorieff N, Gundersen GG, Goode BL. Adenomatous polyposis coli protein nucleates actin assembly and synergizes with the formin mDia1. J Cell Biol 2010; 189:1087-96; PMID:20566685; http://dx.doi.org/10.1083/jcb.201001016.
54. Higashi T, Ikeda T, Murakami T, Shirakawa R, Kawato M, Okawa K, Furuse M, Kimura T, Kita T, Horiuchi H. Flightless-I (Fli-I) regulates the actin assembly activity of diaphanous-related formins (DRFs) Daam1 and mDia1 in cooperation with active Rho GTPase. J Biol Chem 2010; 285:16231-8; PMID:20223827; http://dx.doi.org/10.1074/jbc.M109.079236.
55. Staus DP, Taylor JM, Mack CP. Enhancement of mDia2 activity by Rho-kinase-dependent phosphorylation of the diaphanous autoregulatory domain. Biochem J 2011; 439:57-65; PMID:21699497; http://dx.doi.org/10.1042/BJ20101700.
56. Sun H, Schlondorff J, Higgs HN, Pollak MR. Inverted formin 2 regulates actin dynamics by antagonizing Rho/diaphanous-related formin signaling. J Am Soc Nephrol 2013; 24:917-29; PMID:23620398; http://dx.doi.org/10.1681/ASN.2012080834.
57. Giansanti MG, Bonaccorsi S, Gatti M. The role of anillin in meiotic cytokinesis of Drosophila males. J Cell Sci 1999; 112:2323-34; PMID:10381388.
58. Gönczy P, DiNardo S. The germ line regulates somatic cyst cell proliferation and fate during Drosophila spermatogenesis. Development 1996; 122:2437-47; PMID:8756289.
59. Ucar H, Tachibana K, Kishimoto T. The Mos-MAPK pathway regulates Diaphanous-related formin activity to drive cleavage furrow closure during polar body extrusion in starfish oocytes. J Cell Sci 2013; 126:5153-65; PMID:24046444; http://dx.doi. org/10.1242/jcs.130476.
60. Piekny AJ, Mains PE. Rho-binding kinase (LET-502) and myosin phosphatase (MEL-11) regulate cytokinesis in the early Caenorhabditis elegans embryo. J Cell Sci 2002; 115:2271-82; PMID:12006612.
61. Severson AF, Baillie DL, Bowerman B. A Formin Homology protein and a profilin are required for cytokinesis and Arp2/3-independent assembly of cortical microfilaments in C. elegans. Curr Biol 2002; 12:2066-75; PMID:12498681; http://dx.doi. org/10.1016/S0960-9822(02)01355-6.
62. Swan KA, Severson AF, Carter JC, Martin PR, Schnabel H, Schnabel R, Bowerman B. cyk-1: a C. elegans FH gene required for a late step in embryonic cytokinesis. J Cell Sci 1998; 111:2017-27; PMID:9645949.
63. Kohno H, Tanaka K, Mino A, Umikawa M, Imamura H, Fujiwara T, Fujita Y, Hotta K, Qadota H, Watanabe T, et al. Bni1p implicated in cytoskeletal control is a putative target of Rho1p small GTP binding protein in Saccharomyces cerevisiae. EMBO J 1996; 15:6060-8; PMID:8947028.
64. Webb RL, Zhou MN, McCartney BM. A novel role for an APC2-Diaphanous complex in regulating actin organization in Drosophila. Development 2009; 136:1283-93; PMID:19279137; http://dx.doi. org/10.1242/dev.026963.
65. Watanabe S, Ando Y, Yasuda S, Hosoya H, Watanabe N, Ishizaki T, Narumiya S. mDia2 induces the actin scaffold for the contractile ring and stabilizes its position during cytokinesis in NIH 3T3 cells. Mol Biol Cell 2008; 19:2328-38; PMID:18287523; http://dx.doi.org/10.1091/mbc.E07-10-1086.
66. Zavortink M, Contreras N, Addy T, Bejsovec A, Saint R. Tum/RacGAP50C provides a critical link between anaphase microtubules and the assembly of the contractile ring in Drosophila melanogaster. J Cell Sci 2005; 118:5381-92; PMID:16280552; http://dx.doi. org/10.1242/jcs.02652.
67. Dean SO, Rogers SL, Stuurman N, Vale RD, Spudich JA. Distinct pathways control recruitment and maintenance of myosin II at the cleavage furrow during cytokinesis. Proc Natl Acad Sci U S A 2005; 102:13473-8; PMID:16174742; http://dx.doi.org/10.1073/pnas.0506810102.
68. Kato T, Watanabe N, Morishima Y, Fujita A, Ishizaki T, Narumiya S. Localization of a mammalian homolog of diaphanous, mDia1, to the mitotic spindle in HeLa cells. J Cell Sci 2001; 114:775-84; PMID:11171383.
69. Afshar K, Stuart B, Wasserman SA. Functional analysis of the Drosophila diaphanous FH protein in early embryonic development. Development 2000; 127:1887-97; PMID:10751177.
70. Cao J, Crest J, Fasulo B, Sullivan W. Cortical actin dynamics facilitate early-stage centrosome separation. Curr Biol 2010; 20:770-6; PMID:20409712; http://dx.doi.org/10.1016/j.cub.2010.02.060.
71. Johnston CA, Manning L, Lu MS, Golub O, Doe CQ, Prehoda KE. Formin-mediated actin polymerization cooperates with Mushroom body defect (Mud)-Dynein during Frizzled-Dishevelled spindle orientation. J Cell Sci 2013; 126:4436-44; PMID:23868974; http://dx.doi.org/10.1242/jcs.129544.
72. Cheng L, Zhang J, Ahmad S, Rozier L, Yu H, Deng H, Mao Y. Aurora B regulates formin mDia3 in achieving metaphase chromosome alignment. Dev Cell 2011; 20:342-52; PMID:21397845; http://dx.doi. org/10.1016/j.devcel.2011.01.008.
73. Rundle DR, Gorbsky G, Tsiokas L. PKD2 interacts and co-localizes with mDia1 to mitotic spindles of dividing cells: role of mDia1 IN PKD2 localization to mitotic spindles. J Biol Chem 2004; 279:29728-39; PMID:15123714; http://dx.doi.org/10.1074/jbc. M400544200.
74. Narumiya S, Oceguera-Yanez F, Yasuda S. A new look at Rho GTPases in cell cycle: role in kinetochoremicrotubule attachment. Cell Cycle 2004; 3:855-7; PMID:15190208; http://dx.doi.org/10.4161/cc.3.7.990.
75. Yasuda S, Oceguera-Yanez F, Kato T, Okamoto M, Yonemura S, Terada Y, Ishizaki T, Narumiya S. Cdc42 and mDia3 regulate microtubule attachment to kinetochores. Nature 2004; 428:767-71; PMID:15085137; http://dx.doi.org/10.1038/nature02452.
76. Kyrkou A, Soufi M, Bahtz R, Ferguson C, Bai M, Parton RG, Hoffmann I, Zerial M, Fotsis T, Murphy C. RhoD participates in the regulation of cell-cycle progression and centrosome duplication. Oncogene 2013; 32:1831-42; PMID:22665057; http://dx.doi. org/10.1038/onc.2012.195.
77. Mammoto A, Huang S, Moore K, Oh P, Ingber DE. Role of RhoA, mDia, and ROCK in cell shapedependent control of the Skp2-p27kip1 pathway and the G1/S transition. J Biol Chem 2004; 279:26323-30; PMID:15096506; http://dx.doi.org/10.1074/jbc. M402725200.
78. Beli P, Mascheroni D, Xu D, Innocenti M. WAVE and Arp2/3 jointly inhibit filopodium formation by entering into a complex with mDia2. Nat Cell Biol 2008; 10:849-57; PMID:18516090; http://dx.doi. org/10.1038/ncb1745.
79. Yang C, Czech L, Gerboth S, Kojima S, Scita G, Svitkina T. Novel roles of formin mDia2 in lamellipodia and filopodia formation in motile cells. PLoS Biol 2007; 5:e317; PMID:18044991; http://dx.doi. org/10.1371/journal.pbio.0050317.
80. Goh WI, Ahmed S. mDia1-3 in mammalian filopodia. Commun Integr Biol 2012; 5:340-4; PMID:23060957; http://dx.doi.org/10.4161/cib.20214.
81. Goh WI, Lim KB, Sudhaharan T, Sem KP, Bu W, Chou AM, Ahmed S. mDia1 and WAVE2 proteins interact directly with IRSp53 in filopodia and are involved in filopodium formation. J Biol Chem 2012; 287:4702-14; PMID:22179776; http://dx.doi. org/10.1074/jbc.M111.305102.
82. Mellor H. The role of formins in filopodia formation. Biochim Biophys Acta 2010; 1803:191-200; PMID:19171166; http://dx.doi.org/10.1016/j. bbamcr.2008.12.018.
83. Homem CC, Peifer M. Diaphanous regulates myosin and adherens junctions to control cell contractility and protrusive behavior during morphogenesis. Development 2008; 135:1005-18; PMID:18256194; http://dx.doi.org/10.1242/dev.016337.
84. Maruoka M, Sato M, Yuan Y, Ichiba M, Fujii R, Ogawa T, Ishida-Kitagawa N, Takeya T, Watanabe N. Abl-1-bridged tyrosine phosphorylation of VASP by Abelson kinase impairs association of VASP to focal adhesions and regulates leukaemic cell adhesion. Biochem J 2012; 441:889-99; PMID:22014333; http://dx.doi. org/10.1042/BJ20110951.
85. Svitkina TM, Bulanova EA, Chaga OY, Vignjevic DM, Kojima S, Vasiliev JM, Borisy GG. Mechanism of filopodia initiation by reorganization of a dendritic network. J Cell Biol 2003; 160:409-21; PMID:12566431; http://dx.doi.org/10.1083/jcb.200210174.
86. Shinohara R, Thumkeo D, Kamijo H, Kaneko N, Sawamoto K, Watanabe K, Takebayashi H, Kiyonari H, Ishizaki T, Furuyashiki T, et al. A role for mDia, a Rho-regulated actin nucleator, in tangential migration of interneuron precursors. Nat Neurosci 2012; 15:373-80, S1-2; PMID:22246438; http://dx.doi. org/10.1038/nn.3020.
87. Goulimari P, Kitzing TM, Knieling H, Brandt DT, Offermanns S, Grosse R. Galpha12/13 is essential for directed cell migration and localized Rho-Dia1 function. J Biol Chem 2005; 280:42242-51; PMID:16251183; http://dx.doi.org/10.1074/jbc. M508690200.
88. Gupton SL, Gertler FB. Filopodia: the fingers that do the walking. Sci STKE 2007; 2007:re5; PMID:17712139; http://dx.doi.org/10.1126/stke.4002007re5.
89. Levayer R, Pelissier-Monier A, Lecuit T. Spatial regulation of Dia and Myosin-II by RhoGEF2 controls initiation of E-cadherin endocytosis during epithelial morphogenesis. Nat Cell Biol 2011; 13:529-40; PMID:21516109; http://dx.doi.org/10.1038/ncb2224.
90. Fricke R, Gohl C, Dharmalingam E, Grevelhörster A, Zahedi B, Harden N, Kessels M, Qualmann B, Bogdan S. Drosophila Cip4/Toca-1 integrates membrane trafficking and actin dynamics through WASP and SCAR/WAVE. Curr Biol 2009; 19:1429-37; PMID:19716703; http://dx.doi.org/10.1016/j. cub.2009.07.058.
91. Leibfried A, Fricke R, Morgan MJ, Bogdan S, Bellaiche Y. Drosophila Cip4 and WASp define a branch of the Cdc42-Par6-aPKC pathway regulating E-cadherin endocytosis. Curr Biol 2008; 18:1639-48; PMID:18976911; http://dx.doi.org/10.1016/j. cub.2008.09.063.
92. Fricke R, Gohl C, Bogdan S. The F-BAR protein family Actin' on the membrane. Commun Integr Biol 2010; 3:89-94; PMID:20585497; http://dx.doi. org/10.4161/cib.3.2.10521.
93. Wallar BJ, Deward AD, Resau JH, Alberts AS. RhoB and the mammalian Diaphanous-related formin mDia2 in endosome trafficking. Exp Cell Res 2007; 313:560-71; PMID:17198702; http://dx.doi. org/10.1016/j.yexcr.2006.10.033.
94. Wallar BJ, Stropich BN, Schoenherr JA, Holman HA, Kitchen SM, Alberts AS. The basic region of the diaphanous-autoregulatory domain (DAD) is required for autoregulatory interactions with the diaphanousrelated formin inhibitory domain. J Biol Chem 2006; 281:4300-7; PMID:16361707; http://dx.doi. org/10.1074/jbc.M510277200.
95. Fernandez-Borja M, Janssen L, Verwoerd D, Hordijk P, Neefjes J. RhoB regulates endosome transport by promoting actin assembly on endosomal membranes through Dia1. J Cell Sci 2005; 118:2661-70; PMID:15944396; http://dx.doi.org/10.1242/jcs.02384.
96. Echarri A, Muriel O, Pavón DM, Azegrouz H, Escolar F, Terrón MC, Sanchez-Cabo F, Martínez F, Montoya MC, Llorca O, et al. Caveolar domain organization and trafficking is regulated by Abl kinases and mDia1. J Cell Sci 2012; 125:3097-113; PMID:22454521; http://dx.doi.org/10.1242/jcs.090134.
97. Zilberman Y, Alieva NO, Miserey-Lenkei S, Lichtenstein A, Kam Z, Sabanay H, Bershadsky A. Involvement of the Rho-mDia1 pathway in the regulation of Golgi complex architecture and dynamics. Mol Biol Cell 2011; 22:2900-11; PMID:21680709; http://dx.doi.org/10.1091/mbc.E11-01-0007.
98. Minin AA, Kulik AV, Gyoeva FK, Li Y, Goshima G, Gelfand VI. Regulation of mitochondria distribution by RhoA and formins. J Cell Sci 2006; 119:659-70; PMID:16434478; http://dx.doi.org/10.1242/jcs.02762.
99. DeWard AD, Alberts AS. Microtubule stabilization: formins assert their independence. Curr Biol 2008; 18:R605-8; PMID:18644336; http://dx.doi. org/10.1016/j.cub.2008.06.001.
100. Ishizaki T, Morishima Y, Okamoto M, Furuyashiki T, Kato T, Narumiya S. Coordination of microtubules and the actin cytoskeleton by the Rho effector mDia1. Nat Cell Biol 2001; 3:8-14; PMID:11146620; http://dx.doi.org/10.1038/35050598.
101. Palazzo AF, Cook TA, Alberts AS, Gundersen GG. mDia mediates Rho-regulated formation and orientation of stable microtubules. Nat Cell Biol 2001; 3:723-9; PMID:11483957; http://dx.doi. org/10.1038/35087035.
102. Wen Y, Eng CH, Schmoranzer J, Cabrera-Poch N, Morris EJ, Chen M, Wallar BJ, Alberts AS, Gundersen GG. EB1 and APC bind to mDia to stabilize microtubules downstream of Rho and promote cell migration. Nat Cell Biol 2004; 6:820-30; PMID:15311282; http://dx.doi.org/10.1038/ncb1160.
103. Eng CH, Huckaba TM, Gundersen GG. The formin mDia regulates GSK3beta through novel PKCs to promote microtubule stabilization but not MTOC reorientation in migrating fibroblasts. Mol Biol Cell 2006; 17:5004-16; PMID:16987962; http://dx.doi. org/10.1091/mbc.E05-10-0914.
104. Bartolini F, Moseley JB, Schmoranzer J, Cassimeris L, Goode BL, Gundersen GG. The formin mDia2 stabilizes microtubules independently of its actin nucleation activity. J Cell Biol 2008; 181:523-36; PMID:18458159; http://dx.doi.org/10.1083/jcb.200709029.
105. Bartolini F, Ramalingam N, Gundersen GG. Actincapping protein promotes microtubule stability by antagonizing the actin activity of mDia1. Mol Biol Cell 2012; 23:4032-40; PMID:22918941; http://dx.doi. org/10.1091/mbc.E12-05-0338.
106. Gaillard J, Ramabhadran V, Neumanne E, Gurel P, Blanchoin L, Vantard M, Higgs HN. Differential interactions of the formins INF2, mDia1, and mDia2 with microtubules. Mol Biol Cell 2011; 22:4575-87; PMID:21998204; http://dx.doi.org/10.1091/mbc. E11-07-0616.
107. Gundersen GG, Bulinski JC. Selective stabilization of microtubules oriented toward the direction of cell migration. Proc Natl Acad Sci U S A 1988; 85:5946-50; PMID:3413068; http://dx.doi.org/10.1073/pnas.85.16.5946.
108. Lai SL, Chan TH, Lin MJ, Huang WP, Lou SW, Lee SJ. Diaphanous-related formin 2 and profilin I are required for gastrulation cell movements. PLoS One 2008; 3:e3439; PMID:18941507; http://dx.doi. org/10.1371/journal.pone.0003439.
109. Zhu S, Liu L, Korzh V, Gong Z, Low BC. RhoA acts downstream of Wnt5 and Wnt11 to regulate convergence and extension movements by involving effectors Rho kinase and Diaphanous: use of zebrafish as an in vivo model for GTPase signaling. Cell Signal 2006; 18:359-72; PMID:16019189; http://dx.doi. org/10.1016/j.cellsig.2005.05.019.
110. Grosshans J, Wenzl C, Herz HM, Bartoszewski S, Schnorrer F, Vogt N, Schwarz H, Müller HA. RhoGEF2 and the formin Dia control the formation of the furrow canal by directed actin assembly during Drosophila cellularisation. Development 2005; 132:1009-20; PMID:15689371; http://dx.doi. org/10.1242/dev.01669.
111. Grevengoed EE, Fox DT, Gates J, Peifer M. Balancing different types of actin polymerization at distinct sites: roles for Abelson kinase and Enabled. J Cell Biol 2003; 163:1267-79; PMID:14676307; http://dx.doi. org/10.1083/jcb.200307026.
112. Mason FM, Tworoger M, Martin AC. Apical domain polarization localizes actin-myosin activity to drive ratchet-like apical constriction. Nat Cell Biol 2013; 15:926-36; PMID:23831726; http://dx.doi.org/10.1038/ncb2796.
113. Cavey M, Rauzi M, Lenne PF, Lecuit T. A twotiered mechanism for stabilization and immobilization of E-cadherin. Nature 2008; 453:751-6; PMID:18480755; http://dx.doi.org/10.1038/nature06953.
114. Mulinari S, Barmchi MP, Häcker U. DRhoGEF2 and diaphanous regulate contractile force during segmental groove morphogenesis in the Drosophila embryo. Mol Biol Cell 2008; 19:1883-92; PMID:18287521; http://dx.doi.org/10.1091/mbc. E07-12-1230.
115. Warner SJ, Longmore GD. Distinct functions for Rho1 in maintaining adherens junctions and apical tension in remodeling epithelia. J Cell Biol 2009; 185:1111-25; PMID:19506041; http://dx.doi. org/10.1083/jcb.200901029.
116. Ayollo DV, Zhitnyak IY, Vasiliev JM, Gloushankova NA. Rearrangements of the actin cytoskeleton and E-cadherin-based adherens junctions caused by neoplasic transformation change cell-cell interactions. PLoS One 2009; 4:e8027; PMID:19956566; http://dx.doi.org/10.1371/journal.pone.0008027.
117. Sahai E, Marshall CJ. ROCK and Dia have opposing effects on adherens junctions downstream of Rho. Nat Cell Biol 2002; 4:408-15; PMID:11992112; http://dx.doi.org/10.1038/ncb796.
118. Nakano K, Takaishi K, Kodama A, Mammoto A, Shiozaki H, Monden M, Takai Y. Distinct actions and cooperative roles of ROCK and mDia in Rho small G protein-induced reorganization of the actin cytoskeleton in Madin-Darby canine kidney cells. Mol Biol Cell 1999; 10:2481-91; PMID:10436006; http://dx.doi.org/10.1091/mbc.10.8.2481.
119. Thumkeo D, Shinohara R, Watanabe K, Takebayashi H, Toyoda Y, Tohyama K, Ishizaki T, Furuyashiki T, Narumiya S. Deficiency of mDia, an actin nucleator, disrupts integrity of neuroepithelium and causes periventricular dysplasia. PLoS One 2011; 6:e25465; PMID:21980468; http://dx.doi. org/10.1371/journal.pone.0025465.
120. Massarwa R, Schejter ED, Shilo BZ. Apical secretion in epithelial tubes of the Drosophila embryo is directed by the Formin-family protein Diaphanous. Dev Cell 2009; 16:877-88; PMID:19531358; http://dx.doi.org/10.1016/j.devcel.2009.04.010.
121. Pawson C, Eaton BA, Davis GW. Formin-dependent synaptic growth: evidence that Dlar signals via Diaphanous to modulate synaptic actin and dynamic pioneer microtubules. J Neurosci 2008; 28:11111-23; PMID:18971454; http://dx.doi.org/10.1523/JNEUROSCI.0833-08.2008.
122. Tanizaki H, Egawa G, Inaba K, Honda T, Nakajima S, Moniaga CS, Otsuka A, Ishizaki T, Tomura M, Watanabe T, et al. Rho-mDia1 pathway is required for adhesion, migration, and T-cell stimulation in dendritic cells. Blood 2010; 116:5875-84; PMID:20881208; http://dx.doi.org/10.1182/blood-2010-01-264150.
123. Delon I, Brown NH. The integrin adhesion complex changes its composition and function during morphogenesis of an epithelium. J Cell Sci 2009; 122:4363-74; PMID:19903692; http://dx.doi. org/10.1242/jcs.055996.
124. Bershadsky AD, Ballestrem C, Carramusa L, Zilberman Y, Gilquin B, Khochbin S, Alexandrova AY, Verkhovsky AB, Shemesh T, Kozlov MM. Assembly and mechanosensory function of focal adhesions: experiments and models. Eur J Cell Biol 2006; 85:165-73; PMID:16360240; http://dx.doi. org/10.1016/j.ejcb.2005.11.001.
125. Rao MV, Chu PH, Hahn KM, Zaidel-Bar R. An optogenetic tool for the activation of endogenous diaphanous-related formins induces thickening of stress fibers without an increase in contractility. Cytoskeleton (Hoboken) 2013; 70:394-407; PMID:23677607; http://dx.doi.org/10.1002/cm.21115.
126. Fan L, Pellegrin S, Scott A, Mellor H. The small GTPase Rif is an alternative trigger for the formation of actin stress fibers in epithelial cells. J Cell Sci 2010; 123:1247-52; PMID:20233848; http://dx.doi. org/10.1242/jcs.061754.
127. Hotulainen P, Lappalainen P. Stress fibers are generated by two distinct actin assembly mechanisms in motile cells. J Cell Biol 2006; 173:383-94; PMID:16651381; http://dx.doi.org/10.1083/jcb.200511093.
128. Anderson S, DiCesare L, Tan I, Leung T, SundarRaj N. Rho-mediated assembly of stress fibers is differentially regulated in corneal fibroblasts and myofibroblasts. Exp Cell Res 2004; 298:574-83; PMID:15265703; http://dx.doi.org/10.1016/j.yexcr.2004.05.005.
129. Baarlink C, Wang H, Grosse R. Nuclear actin network assembly by formins regulates the SRF coactivator MAL. Science 2013; 340:864-7; PMID:23558171; http://dx.doi.org/10.1126/science.1235038.
130. Copeland JW, Treisman R. The diaphanous-related formin mDia1 controls serum response factor activity through its effects on actin polymerization. Mol Biol Cell 2002; 13:4088-99; PMID:12429848; http://dx.doi.org/10.1091/mbc.02-06-0092.
131. Geneste O, Copeland JW, Treisman R. LIM kinase and Diaphanous cooperate to regulate serum response factor and actin dynamics. J Cell Biol 2002; 157:831-8; PMID:12034774; http://dx.doi.org/10.1083/jcb.200203126.
132. Tominaga T, Sahai E, Chardin P, McCormick F, Courtneidge SA, Alberts AS. Diaphanous-related formins bridge Rho GTPase and Src tyrosine kinase signaling. Mol Cell 2000; 5:13-25; PMID:10678165; http://dx.doi.org/10.1016/S1097-2765(00)80399-8.
133. Chan MW, Chaudary F, Lee W, Copeland JW, McCulloch CA. Force-induced myofibroblast differentiation through collagen receptors is dependent on mammalian diaphanous (mDia). J Biol Chem 2010; 285:9273-81; PMID:20071339; http://dx.doi. org/10.1074/jbc.M109.075218.
134. Somogyi K, Rørth P. Evidence for tension-based regulation of Drosophila MAL and SRF during invasive cell migration. Dev Cell 2004; 7:85-93; PMID:15239956; http://dx.doi.org/10.1016/j.devcel.2004.05.020.
135. Riveline D, Zamir E, Balaban NQ, Schwarz US, Ishizaki T, Narumiya S, Kam Z, Geiger B, Bershadsky AD. Focal contacts as mechanosensors: externally applied local mechanical force induces growth of focal contacts by an mDia1-dependent and ROCKindependent mechanism. J Cell Biol 2001; 153:1175-86; PMID:11402062; http://dx.doi.org/10.1083/jcb.153.6.1175.
136. Higashida C, Kiuchi T, Akiba Y, Mizuno H, Maruoka M, Narumiya S, Mizuno K, Watanabe N. F-and G-actin homeostasis regulates mechanosensitive actin nucleation by formins. Nat Cell Biol 2013; 15:395-405; PMID:23455479; http://dx.doi.org/10.1038/ncb2693.
137. Shemesh T, Geiger B, Bershadsky AD, Kozlov MM. Focal adhesions as mechanosensors: a physical mechanism. Proc Natl Acad Sci U S A 2005; 102:12383-8; PMID:16113084; http://dx.doi.org/10.1073/pnas.0500254102.
138. Kozlov MM, Bershadsky AD. Processive capping by formin suggests a force-driven mechanism of actin polymerization. J Cell Biol 2004; 167:1011-7; PMID:15596547; http://dx.doi.org/10.1083/jcb.200410017.
139. Jégou A, Carlier MF, Romet-Lemonne G. Formin mDia1 senses and generates mechanical forces on actin filaments. Nat Commun 2013; 4:1883; PMID:23695677; http://dx.doi.org/10.1038/ncomms2888.
140. Courtemanche N, Lee JY, Pollard TD, Greene EC. Tension modulates actin filament polymerization mediated by formin and profilin. Proc Natl Acad Sci U S A 2013; 110:9752-7; PMID:23716666; http://dx.doi.org/10.1073/pnas.1308257110.
141. Tamura K, Mizutani T, Haga H, Kawabata K. Nanomechanical properties of living cells expressing constitutively active RhoA effectors. Biochem Biophys Res Commun 2010; 403:363-7; PMID:21078298; http://dx.doi.org/10.1016/j.bbrc.2010.11.036.
142. Lalwani AK, Jackler RK, Sweetow RW, Lynch ED, Raventós H, Morrow J, King MC, León PE. Further characterization of the DFNA1 audiovestibular phenotype. Arch Otolaryngol Head Neck Surg 1998; 124:699-702; PMID:9639482; http://dx.doi. org/10.1001/archotol.124.6.699.
143. Lynch ED, Lee MK, Morrow JE, Welcsh PL, León PE, King MC. Nonsyndromic deafness DFNA1 associated with mutation of a human homolog of the Drosophila gene diaphanous. Science 1997; 278:1315-8; PMID:9360932; http://dx.doi.org/10.1126/science.278.5341.1315.
144. Cosetti M, Culang D, Kotla S, O'Brien P, Eberl DF, Hannan F. Unique transgenic animal model for hereditary hearing loss. Ann Otol Rhinol Laryngol 2008; 117:827-33; PMID:19102128.
145. Schoen CJ, Burmeister M, Lesperance MM. Diaphanous homolog 3 (Diap3) overexpression causes progressive hearing loss and inner hair cell defects in a transgenic mouse model of human deafness. PLoS One 2013; 8:e56520; PMID:23441200; http://dx.doi. org/10.1371/journal.pone.0056520.
146. Schoen CJ, Emery SB, Thorne MC, Ammana HR, Sliwerska E, Arnett J, Hortsch M, Hannan F, Burmeister M, Lesperance MM. Increased activity of Diaphanous homolog 3 (DIAPH3)/diaphanous causes hearing defects in humans with auditory neuropathy and in Drosophila. Proc Natl Acad Sci U S A 2010; 107:13396-401; PMID:20624953; http://dx.doi. org/10.1073/pnas.1003027107.
147. Bione S, Sala C, Manzini C, Arrigo G, Zuffardi O, Banfi S, Borsani G, Jonveaux P, Philippe C, Zuccotti M, et al. A human homologue of the Drosophila melanogaster diaphanous gene is disrupted in a patient with premature ovarian failure: evidence for conserved function in oogenesis and implications for human sterility. Am J Hum Genet 1998; 62:533-41; PMID:9497258; http://dx.doi.org/10.1086/301761.
148. Shi Y, Dong B, Miliotis H, Liu J, Alberts AS, Zhang J, Siminovitch KA. Src kinase Hck association with the WASp and mDia1 cytoskeletal regulators promotes chemoattractant-induced Hck membrane targeting and activation in neutrophils. Biochem Cell Biol 2009; 87:207-16; PMID:19234535; http://dx.doi. org/10.1139/O08-130.
149. Shi Y, Zhang J, Mullin M, Dong B, Alberts AS, Siminovitch KA. The mDial formin is required for neutrophil polarization, migration, and activation of the LARG/RhoA/ROCK signaling axis during chemotaxis. J Immunol 2009; 182:3837-45; PMID:19265163; http://dx.doi.org/10.4049/jimmunol.0803838.
150. Sakata D, Taniguchi H, Yasuda S, Adachi-Morishima A, Hamazaki Y, Nakayama R, Miki T, Minato N, Narumiya S. Impaired T lymphocyte trafficking in mice deficient in an actin-nucleating protein, mDia1. J Exp Med 2007; 204:2031-8; PMID:17682067; http://dx.doi.org/10.1084/jem.20062647.
151. Vicente-Manzanares M, Rey M, Pérez-Martínez M, Yáñez-Mó M, Sancho D, Cabrero JR, Barreiro O, de la Fuente H, Itoh K, Sánchez-Madrid F. The RhoA effector mDia is induced during T cell activation and regulates actin polymerization and cell migration in T lymphocytes. J Immunol 2003; 171:1023-34; PMID:12847276.
152. Ji P, Jayapal SR, Lodish HF. Enucleation of cultured mouse fetal erythroblasts requires Rac GTPases and mDia2. Nat Cell Biol 2008; 10:314-21; PMID:18264091; http://dx.doi.org/10.1038/ncb1693.
153. Gao GX, Dong HJ, Gu HT, Gao Y, Pan YZ, Wang YW, Yang Y, Chen XQ. [PI3-kinase mediates thrombin-induced platelet aggregation through mDia1 pathway.]. Zhonghua Xue Ye Xue Za Zhi 2010; 31:176-80; PMID:20510108.
154. Higashi T, Ikeda T, Shirakawa R, Kondo H, Kawato M, Horiguchi M, Okuda T, Okawa K, Fukai S, Nureki O, et al. Biochemical characterization of the Rho GTPase-regulated actin assembly by diaphanousrelated formins, mDia1 and Daam1, in platelets. J Biol Chem 2008; 283:8746-55; PMID:18218625; http://dx.doi.org/10.1074/jbc.M707839200.
155. Naj X, Hoffmann AK, Himmel M, Linder S. The formins FMNL1 and mDia1 regulate coiling phagocytosis of Borrelia burgdorferi by primary human macrophages. Infect Immun 2013; 81:1683-95; PMID:23460512; http://dx.doi.org/10.1128/IAI.01411-12.
156. Colucci-Guyon E, Niedergang F, Wallar BJ, Peng J, Alberts AS, Chavrier P. A role for mammalian diaphanous-related formins in complement receptor (CR3)-mediated phagocytosis in macrophages. Curr Biol 2005; 15:2007-12; PMID:16303559; http://dx.doi. org/10.1016/j.cub.2005.09.051.
157. Heindl JE, Saran I, Yi CR, Lesser CF, Goldberg MB. Requirement for formin-induced actin polymerization during spread of Shigella flexneri. Infect Immun 2010; 78:193-203; PMID:19841078; http://dx.doi. org/10.1128/IAI.00252-09.
158. Alto NM, Shao F, Lazar CS, Brost RL, Chua G, Mattoo S, McMahon SA, Ghosh P, Hughes TR, Boone C, et al. Identification of a bacterial type III effector family with G protein mimicry functions. Cell 2006; 124:133-45; PMID:16413487; http://dx.doi. org/10.1016/j.cell.2005.10.031.
159. Li D, Dammer EB, Lucki NC, Sewer MB. cAMPstimulated phosphorylation of diaphanous 1 regulates protein stability and interaction with binding partners in adrenocortical cells. Mol Biol Cell 2013; 24:848-57; PMID:23325789; http://dx.doi.org/10.1091/mbc. E12-08-0597.
160. Li D, Sewer MB. RhoA and DIAPH1 mediate adrenocorticotropin-stimulated cortisol biosynthesis by regulating mitochondrial trafficking. Endocrinology 2010; 151:4313-23; PMID:20591975; http://dx.doi. org/10.1210/en.2010-0044.
161. Tsujita K, Itoh T, Kondo A, Oyama M, Kozuka-Hata H, Irino Y, Hasegawa J, Takenawa T. Proteome of acidic phospholipid-binding proteins: spatial and temporal regulation of Coronin 1A by phosphoinositides. J Biol Chem 2010; 285:6781-9; PMID:20032464; http://dx.doi.org/10.1074/jbc.M109.057018.
162. Lim KB, Bu W, Goh WI, Koh E, Ong SH, Pawson T, Sudhaharan T, Ahmed S. The Cdc42 effector IRSp53 generates filopodia by coupling membrane protrusion with actin dynamics. J Biol Chem 2008; 283:20454-72; PMID:18448434; http://dx.doi.org/10.1074/jbc. M710185200.
163. Meng W, Numazaki M, Takeuchi K, Uchibori Y, Ando-Akatsuka Y, Tominaga M, Tominaga T. DIP (mDia interacting protein) is a key molecule regulating Rho and Rac in a Src-dependent manner. EMBO J 2004; 23:760-71; PMID:14765113; http://dx.doi. org/10.1038/sj.emboj.7600095.
164. Fukumi-Tominaga T, Mori Y, Matsuura A, Kaneko K, Matsui M, Ogata M, Tominaga M. DIP/WISHdeficient mice reveal Dia-and N-WASP-interacting protein as a regulator of cytoskeletal dynamics in embryonic fibroblasts. Genes Cells 2009; 14:1197-207; PMID:19778379; http://dx.doi. org/10.1111/j.1365-2443.2009.01345.x.
165. Wyse MM, Lei J, Nestor-Kalinoski AL, Eisenmann KM. Dia-interacting protein (DIP) imposes migratory plasticity in mDia2-dependent tumor cells in threedimensional matrices. PLoS One 2012; 7:e45085; PMID:23024796; http://dx.doi.org/10.1371/journal. pone.0045085.
166. Touré F, Fritz G, Li Q, Rai V, Daffu G, Zou YS, Rosario R, Ramasamy R, Alberts AS, Yan SF, et al. Formin mDia1 mediates vascular remodeling via integration of oxidative and signal transduction pathways. Circ Res 2012; 110:1279-93; PMID:22511750; http://dx.doi.org/10.1161/CIRCRESAHA.111.262519.
167. Wickström SA, Lange A, Hess MW, Polleux J, Spatz JP, Krüger M, Pfaller K, Lambacher A, Bloch W, Mann M, et al. Integrin-linked kinase controls microtubule dynamics required for plasma membrane targeting of caveolae. Dev Cell 2010; 19:574-88; PMID:20951348; http://dx.doi.org/10.1016/j.devcel.2010.09.007.
168. Sun H, Schlondorff JS, Brown EJ, Higgs HN, Pollak MR. Rho activation of mDia formins is modulated by an interaction with inverted formin 2 (INF2). Proc Natl Acad Sci U S A 2011; 108:2933-8; PMID:21278336; http://dx.doi.org/10.1073/pnas.1017010108.
169. Destaing O, Saltel F, Gilquin B, Chabadel A, Khochbin S, Ory S, Jurdic P. A novel Rho-mDia2-HDAC6 pathway controls podosome patterning through microtubule acetylation in osteoclasts. J Cell Sci 2005; 118:2901-11; PMID:15976449; http://dx.doi.org/10.1242/jcs.02425.
170. Stüven T, Hartmann E, Görlich D. Exportin 6: a novel nuclear export receptor that is specific for profilin. actin complexes. EMBO J 2003; 22:5928-40; PMID:14592989; http://dx.doi.org/10.1093/emboj/cdg565.
171. Miki T, Okawa K, Sekimoto T, Yoneda Y, Watanabe S, Ishizaki T, Narumiya S. mDia2 shuttles between the nucleus and the cytoplasm through the importinalpha/beta-and CRM1-mediated nuclear transport mechanism. J Biol Chem 2009; 284:5753-62; PMID:19117945; http://dx.doi.org/10.1074/jbc. M806191200.
172. Punta M, Coggill PC, Eberhardt RY, Mistry J, Tate J, Boursnell C, Pang N, Forslund K, Ceric G, Clements J, et al. The Pfam protein families database. Nucleic Acids Res 2012; 40:D290-301; PMID:22127870; http://dx.doi.org/10.1093/nar/gkr1065.
173. Guindon S, Gascuel O. A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood. Syst Biol 2003; 52:696-704; PMID:14530136; http://dx.doi.org/10.1080/10635150390235520.
174. Anisimova M, Gascuel O. Approximate likelihood-ratio test for branches: A fast, accurate, and powerful alternative. Syst Biol 2006; 55:539-52; PMID:16785212; http://dx.doi.org/10.1080/10635150600755453.