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Unleashing formins to remodel the actin and microtubule cytoskeletons

Key Points

  • Formins are a large family of conserved proteins, defined by the presence of formin homology 1 (FH1) and FH2 domains, that directly stimulate actin assembly. Outside of these domains, formins show wide variation in their sequences, which specify key differences in their regulation.

  • Formins promote de novo actin assembly, and their FH2 domains remain processively attached to the elongating end of the filament. Through interactions of their FH1 domains with profilin–actin, formins accelerate, to different degrees, actin addition at filament ends.

  • Recent work has shown that some formins also regulate microtubule dynamics in vivo and in vitro, but the specific mechanistic role of formins in this capacity is yet to be determined.

  • Emerging evidence suggests that formin activities are regulated in vivo at multiple points, including the initial recruitment and activation of formins at membranes, actin nucleation and elongation, and the displacement, inactivation, recycling and turnover of formins.

  • A growing list of formin binding partners has been implicated in the regulation of formin activities, suggesting that multiple signalling pathways converge on formins to trigger cytoskeletal remodelling. Further work is required to elucidate their mechanisms and understand how formins are harnessed to different cellular tasks.

Abstract

Formins are highly conserved proteins that have essential roles in remodelling the actin and microtubule cytoskeletons to influence eukaryotic cell shape and behaviour. Recent work has identified numerous cellular factors that locally recruit, activate or inactivate formins to bridle and unleash their potent effects on actin nucleation and elongation. The effects of formins on microtubules have also begun to be described, which places formins in a prime position to coordinate actin and microtubule dynamics. The emerging complexity in the mechanisms governing formins mirrors the wide range of essential functions that they perform in cell motility, cell division and cell and tissue morphogenesis.

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Figure 1: Cellular structures and functions controlled by formins.
Figure 2: Domain organization of autoinhibited formins.
Figure 3: Proposed model of regulatory points in the formin activity cycle.

References

  1. Goode, B. L. & Eck, M. J. Mechanism and function of formins in the control of actin assembly. Annu. Rev. Biochem. 76, 593–627 (2007).

    CAS  PubMed  Google Scholar 

  2. DeWard, A. D. & Alberts, A. S. Microtubule stabilization: formins assert their independence. Curr. Biol. 18, 605–608 (2008).

    Google Scholar 

  3. Chesarone, M. A. & Goode, B. L. Actin nucleation and elongation factors: mechanisms and interplay. Curr. Opin. Cell Biol. 21, 28–37 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Zuchero, J. B., Coutts, A. S., Quinlan, M. E., Thangue, N. B. & Mullins, R. D. p53-cofactor JMY is a multifunctional actin nucleation factor. Nature Cell Biol. 11, 451–459 (2009).

    CAS  PubMed  Google Scholar 

  5. Higgs, H. N. Formin proteins: a domain-based approach. Trends Biochem. Sci. 30, 342–353 (2005).

    CAS  PubMed  Google Scholar 

  6. Grunt, M., Zarsky, V. & Cvrckova, F. Roots of angiosperm formins: the evolutionary history of plant FH2 domain-containing proteins. BMC Evol. Biol. 8, 115 (2008).

    PubMed  PubMed Central  Google Scholar 

  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. 25, 2717–2733 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Perelroizen, I., Marchand, J. B., Blanchoin, L., Didry, D. & Carlier, M. F. Interaction of profilin with G-actin and poly(L-proline). Biochemistry 33, 8472–8478 (1994).

    CAS  PubMed  Google Scholar 

  9. Schutt, C. E., Myslik, J. C., Rozycki, M. D., Goonesekere, N. C. & Lindberg, U. The structure of crystalline profilin-β-actin. Nature 365, 810–816 (1993).

    CAS  PubMed  Google Scholar 

  10. Kursula, P. et al. High-resolution 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. 375, 270–290 (2008).

    CAS  PubMed  Google Scholar 

  11. Kaiser, D. A., Vinson, V. K., Murphy, D. B. & Pollard, T. D. Profilin is predominantly associated with monomeric actin in Acanthamoeba. J. Cell Sci. 112, 3779–3790 (1999).

    CAS  PubMed  Google Scholar 

  12. Kovar, D. R., Kuhn, J. R., Tichy, A. L. & Pollard, T. D. The fission yeast cytokinesis formin Cdc12p is a barbed end actin filament capping protein gated by profilin. J. Cell Biol. 161, 875–887 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Yonetani, A. et al. Regulation and targeting of the fission yeast formin Cdc12p in cytokinesis. Mol. Biol. Cell 19, 2208–2219 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Sagot, I., Rodal, A. A., Moseley, J., Goode, B. L. & Pellman, D. An actin nucleation mechanism mediated by Bni1 and profilin. Nature Cell Biol. 4, 626–631 (2002). Together with reference 46, this study was the first to show that formins directly nucleate actin polymerization, and that formin interactions with profilin–actin complexes further stimulate actin assembly.

    CAS  PubMed  Google Scholar 

  15. Paul, A. S. & Pollard, T. D. Energetic requirements for processive elongation of actin filaments by FH1FH2-formins. J. Biol. Chem. 284, 12533–12540 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Wen, Y. et al. EB1 and APC bind to mDia to stabilize microtubules downstream of Rho and promote cell migration. Nature Cell Biol. 6, 820–830 (2004).

    CAS  PubMed  Google Scholar 

  17. Lewkowicz, E. et al. The microtubule-binding protein CLIP-170 coordinates mDia1 and actin reorganization during CR3-mediated phagocytosis. J. Cell Biol. 183, 1287–1298 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Bartolini, F. et al. The formin mDia2 stabilizes microtubules independently of its actin nucleation activity. J. Cell Biol. 181, 523–536 (2008). This study was the first to show that formin effects on microtubules, both in vitro and in vivo , can be genetically uncoupled from their effects on actin assembly.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Higgs, H. N. & Peterson, K. J. Phylogenetic analysis of the formin homology 2 domain. Mol. Biol. Cell 16, 1–13 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Rose, R. et al. Structural and mechanistic insights into the interaction between Rho and mammalian Dia. Nature 435, 513–518 (2005).

    CAS  PubMed  Google Scholar 

  21. Otomo, T., Otomo, C., Tomchick, D. R., Machius, M. & Rosen, M. K. Structural basis of Rho GTPase-mediated activation of the formin mDia1. Mol. Cell 18, 273–281 (2005).

    CAS  PubMed  Google Scholar 

  22. Nezami, A. G., Poy, F. & Eck, M. J. Structure of the autoinhibitory switch in formin mDia1. Structure 14, 257–263 (2006).

    CAS  PubMed  Google Scholar 

  23. Lammers, M., Meyer, S., Kuhlmann, D. & Wittinghofer, A. Specificity of interactions between mDia isoforms and Rho proteins. J. Biol. Chem. 283, 35236–35246 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Schonichen, A. et al. Biochemical characterization of the diaphanous autoregulatory interaction in the formin homology protein FHOD1. J. Biol. Chem. 281, 5084–5093 (2006).

    PubMed  Google Scholar 

  25. Wallar, B. J. et al. The basic region of the diaphanous-autoregulatory domain (DAD) is required for autoregulatory interactions with the diaphanous-related formin inhibitory domain. J. Biol. Chem. 281, 4300–4307 (2006).

    CAS  PubMed  Google Scholar 

  26. Li, F. & Higgs, H. N. The mouse Formin mDia1 is a potent actin nucleation factor regulated by autoinhibition. Curr. Biol. 13, 1335–1340 (2003). The characterization of mDia1 that provided the first biochemical demonstration of formin autoinhibition through interactions between the N- and C-terminal halves of the protein.

    CAS  PubMed  Google Scholar 

  27. Liu, W. et al. Mechanism of activation of the Formin protein Daam1. Proc. Natl Acad. Sci. USA 105, 210–215 (2008).

    CAS  PubMed  Google Scholar 

  28. Habas, R., Kato, Y. & He, X. Wnt/Frizzled activation of Rho regulates vertebrate gastrulation and requires a novel Formin homology protein Daam1. Cell 107, 843–854 (2001).

    CAS  PubMed  Google Scholar 

  29. Kitzing, T. M. et al. Positive feedback between Dia1, LARG, and RhoA regulates cell morphology and invasion. Genes Dev. 21, 1478–1483 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Miyagi, Y. et al. Delphilin: a novel PDZ and formin homology domain-containing protein that synaptically colocalizes and interacts with glutamate receptor δ2 subunit. J. Neurosci. 22, 803–814 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Matsuda, K., Matsuda, S., Gladding, C. M. & Yuzaki, M. Characterization of the δ2 glutamate receptor-binding protein delphilin: splicing variants with differential palmitoylation and an additional PDZ domain. J. Biol. Chem. 281, 25577–25587 (2006).

    CAS  PubMed  Google Scholar 

  32. Deeks, M. J. et al. Arabidopsis group Ie formins localize to specific cell membrane domains, interact with actin-binding proteins and cause defects in cell expansion upon aberrant expression. New Phytol. 168, 529–540 (2005).

    CAS  PubMed  Google Scholar 

  33. Pring, M., Evangelista, M., Boone, C., Yang, C. & Zigmond, S. H. Mechanism of formin-induced nucleation of actin filaments. Biochemistry 42, 486–496 (2003).

    CAS  PubMed  Google Scholar 

  34. Moseley, J. B. et al. A conserved mechanism for Bni1- and mDia1-induced actin assembly and dual regulation of Bni1 by Bud6 and profilin. Mol. Biol. Cell 15, 896–907 (2004). Characterization of yeast Bni1 and mouse Dia1 formins, showing that formins have a conserved function in protecting the growing barbed ends of actin filaments from capping proteins, that the FH2 domain must dimerize to be active and that Bud6 binds directly to Bni1 to stimulate its actin assembly activity.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Xu, Y. et al. Crystal structures of a formin homology-2 domain reveal a tethered dimer architecture. Cell 116, 711–723 (2004). This study provided the first crystal structure of an active formin molecule, revealing that the FH2 is a flexibly tethered dimer, which led to the 'stair-stepping' model for processive motion of the FH2 on growing barbed ends of actin filaments.

    CAS  PubMed  Google Scholar 

  36. Otomo, T. et al. Structural basis of actin filament nucleation and processive capping by a formin homology 2 domain. Nature 433, 488–494 (2005).

    CAS  PubMed  Google Scholar 

  37. Sept, D. & McCammon, J. A. Thermodynamics and kinetics of actin filament nucleation. Biophys. J. 81, 667–674 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Higashida, C. et al. G-actin regulates rapid induction of actin nucleation by mDia1 to restore cellular actin polymers. J. Cell Sci. 121, 3403–3412 (2008).

    CAS  PubMed  Google Scholar 

  39. Takeya, R., Taniguchi, K., Narumiya, S. & Sumimoto, H. The mammalian formin FHOD1 is activated through phosphorylation by ROCK and mediates thrombin-induced stress fibre formation in endothelial cells. EMBO J. 27, 618–628 (2008). Using complementary in vitro and in vivo approaches, this study showed that phosphorylation of the formin FHOD1 by ROCK disrupts FHOD1 autoinhibition independently of Rho binding and stimulates stress fibre formation.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Hannemann, S. et al. The Diaphanous-related formin FHOD1 associates with ROCK1 and promotes Src-dependent plasma membrane blebbing. J. Biol. Chem. 283, 27891–27903 (2008).

    CAS  PubMed  Google Scholar 

  41. Moseley, J. B. & Goode, B. L. Differential activities and regulation of Saccharomyces cerevisiae formin proteins Bni1 and Bnr1 by Bud6. J. Biol. Chem. 280, 28023–28033 (2005).

    CAS  PubMed  Google Scholar 

  42. Martin, S. G., Rincon, S. A., Basu, R., Perez, P. & Chang, F. Regulation of the formin for3p by cdc42p and bud6p. Mol. Biol. Cell 18, 4155–4167 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Pechlivanis, M., Samol, A. & Kerkhoff, E. Identification of a short Spir interaction sequence at the C-terminal end of formin subgroup proteins. J. Biol. Chem. 284, 25324–25333 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Dahlgaard, K., Raposo, A. A., Niccoli, T. & St. Johnston, D. Capu and Spire assemble a cytoplasmic actin mesh that maintains microtubule organization in the Drosophila oocyte. Dev. Cell 13, 539–553 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Quinlan, M. E., Hilgert, S., Bedrossian, A., Mullins, R. D. & Kerkhoff, E. Regulatory interactions between two actin nucleators, Spire and Cappuccino. J. Cell Biol. 179, 117–128 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Pruyne, D. et al. Role of formins in actin assembly: nucleation and barbed-end association. Science 297, 612–615 (2002). Together with reference 14, this study was the first to show that formins directly nucleate actin polymerization, and showed unexpectedly that formins physically associate with the dynamic barbed ends of actin filaments.

    CAS  PubMed  Google Scholar 

  47. Zigmond, S. H. et al. Formin leaky cap allows elongation in the presence of tight capping proteins. Curr. Biol. 13, 1820–1823 (2003).

    CAS  PubMed  Google Scholar 

  48. Kovar, D. R. & Pollard, T. D. Insertional assembly of actin filament barbed ends in association with formins produces piconewton forces. Proc. Natl Acad. Sci. USA 101, 14725–14730 (2004). This study used TIRF microscopy to visualize in real time polymerizing actin filaments associated with formins at their barbed ends, and found that formins remain persistently attached to the barbed ends while allowing the insertional assembly of new subunits.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Higashida, C. et al. Actin polymerization-driven molecular movement of mDia1 in living cells. Science 303, 2007–2010 (2004). This study used live-cell imaging to track the movements of mDia1–GFP fusion proteins in cultured cells, which revealed rapid and persistent, actin-dependent movements on linear tracks, providing the first in vivo evidence for formins moving processively on growing barbed ends.

    CAS  PubMed  Google Scholar 

  50. Vidali, L. et al. Rapid formin-mediated actin-filament elongation is essential for polarized plant cell growth. Proc. Natl Acad. Sci. USA 106, 13341–13346 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Breitsprecher, D. et al. Clustering of VASP actively drives processive, WH2 domain-mediated actin filament elongation. EMBO J. 27, 2943–2954 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Romero, S. et al. Formin is a processive motor that requires profilin to accelerate actin assembly and associated ATP hydrolysis. Cell 119, 419–429 (2004). This study was the first to report that formins can accelerate elongation at barbed ends, a conclusion that was reached by comparing the lengths of actin filaments assembled in the presence and absence of formins.

    CAS  PubMed  Google Scholar 

  53. Kovar, D. R., Harris, E. S., Mahaffy, R., Higgs, H. N. & Pollard, T. D. Control of the assembly of ATP- and ADP-actin by formins and profilin. Cell 124, 423–435 (2006). This study used TIRF microscopy to show that formins markedly accelerate barbed end elongation through physical interactions between their FH1 domains and profilin–actin complexes, and that different formins support different elongation rates.

    CAS  PubMed  Google Scholar 

  54. Vavylonis, D., Kovar, D. R., O'Shaughnessy, B. & Pollard, T. D. Model of formin-associated actin filament elongation. Mol. Cell 21, 455–466 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Neidt, E. M., Scott, B. J. & Kovar, D. R. Formin differentially utilizes profilin isoforms to rapidly assemble actin filaments. J. Biol. Chem. 284, 673–684 (2009).

    CAS  PubMed  Google Scholar 

  56. Harris, E. S., Rouiller, I., Hanein, D. & Higgs, H. N. Mechanistic differences in actin bundling activity of two mammalian formins, FRL1 and mDia2. J. Biol. Chem. 281, 14383–14392 (2006).

    CAS  PubMed  Google Scholar 

  57. Michelot, A. et al. The formin homology 1 domain modulates the actin nucleation and bundling activity of Arabidopsis FORMIN1. Plant Cell 17, 2296–2313 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Vaillant, D. C. et al. Interaction of the N- and C-terminal autoregulatory domains of FRL2 does not inhibit FRL2 activity. J. Biol. Chem. 283, 33750–33762 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Harris, E. S., Li, F. & Higgs, H. N. The mouse formin, FRLα, slows actin filament barbed end elongation, competes with capping protein, accelerates polymerization from monomers, and severs filaments. J. Biol. Chem. 279, 20076–20087 (2004).

    CAS  PubMed  Google Scholar 

  60. Chhabra, E. S. & Higgs, H. N. INF2 is a WASP homology 2 motif-containing formin that severs actin filaments and accelerates both polymerization and depolymerization. J. Biol. Chem. 281, 26754–26767 (2006).

    CAS  PubMed  Google Scholar 

  61. Yi, K. et al. Cloning and functional characterization of a formin-like protein (AtFH8) from Arabidopsis. Plant Physiol. 138, 1071–1082 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Waterman-Storer, C. M. & Salmon, E. Positive feedback interactions between microtubule and actin dynamics during cell motility. Curr. Opin. Cell Biol. 11, 61–67 (1999).

    CAS  PubMed  Google Scholar 

  63. Goode, B. L., Drubin, D. G. & Barnes, G. Functional cooperation between the microtubule and actin cytoskeletons. Curr. Opin. Cell Biol. 12, 63–71 (2000).

    CAS  PubMed  Google Scholar 

  64. Lin, S. X., Gundersen, G. G. & Maxfield, F. R. Export from pericentriolar endocytic recycling compartment to cell surface depends on stable, detyrosinated (glu) microtubules and kinesin. Mol. Biol. Cell 13, 96–109 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Palazzo, A. F., Cook, T. A., Alberts, A. S. & Gundersen, G. G. mDia mediates Rho-regulated formation and orientation of stable microtubules. Nature Cell Biol. 3, 723–729 (2001). This study was the first to show that formins can bind directly to microtubules and regulate microtubule stability in vivo.

    CAS  PubMed  Google Scholar 

  66. Pawson, C., Eaton, B. A. & Davis, G. W. Formin-dependent synaptic growth: evidence that Dlar signals via Diaphanous to modulate synaptic actin and dynamic pioneer microtubules. J. Neurosci. 28, 11111–11123 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Lee, L., Klee, S. K., Evangelista, M., Boone, C. & Pellman, D. Control of mitotic spindle position by the Saccharomyces cerevisiae formin Bni1p. J. Cell Biol. 144, 947–961 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Delgehyr, N., Lopes, C. S., Moir, C. A., Huisman, S. M. & Segal, M. Dissecting the involvement of formins in Bud6p-mediated cortical capture of microtubules in S. cerevisiae. J. Cell Sci. 121, 3803–3814 (2008).

    CAS  PubMed  Google Scholar 

  69. Yasuda, S. et al. Cdc42 and mDia3 regulate microtubule attachment to kinetochores. Nature 428, 767–771 (2004).

    CAS  PubMed  Google Scholar 

  70. Kaverina, I., Rottner, K. & Small, J. V. Targeting, capture, and stabilization of microtubules at early focal adhesions. J. Cell Biol. 142, 181–190 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Yin, H., Pruyne, D., Huffaker, T. C. & Bretscher, A. Myosin V orientates the mitotic spindle in yeast. Nature 406, 1013–1015 (2000).

    CAS  PubMed  Google Scholar 

  72. Beach, D. L., Thibodeaux, J., Maddox, P., Yeh, E. & Bloom, K. The role of the proteins Kar9 and Myo2 in orienting the mitotic spindle of budding yeast. Curr. Biol. 10, 1497–1506 (2000).

    CAS  PubMed  Google Scholar 

  73. Sider, J. R. et al. Direct observation of microtubule-F-actin interaction in cell free lysates. J. Cell Sci. 112, 1947–1956 (1999).

    CAS  PubMed  Google Scholar 

  74. Young, K. G., Thurston, S. F., Copeland, S., Smallwood, C. & Copeland, J. W. INF1 is a novel microtubule-associated formin. Mol. Biol. Cell 19, 5168–5180 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Rosales-Nieves, A. E. et al. Coordination of microtubule and microfilament dynamics by Drosophila Rho1, Spire and Cappuccino. Nature Cell Biol. 8, 367–376 (2006).

    CAS  PubMed  Google Scholar 

  76. Zhou, F., Leder, P. & Martin, S. S. Formin-1 protein associates with microtubules through a peptide domain encoded by exon-2. Exp. Cell Res. 312, 1119–1126 (2006).

    CAS  PubMed  Google Scholar 

  77. Evangelista, M., Pruyne, D., Amberg, D. C., Boone, C. & Bretscher, A. Formins direct Arp2/3-independent actin filament assembly to polarize cell growth in yeast. Nature Cell Biol. 4, 260–269 (2002).

    CAS  PubMed  Google Scholar 

  78. Watanabe, N., Kato, T., Fujita, A., Ishizaki, T. & Narumiya, S. Cooperation between mDia1 and ROCK in Rho-induced actin reorganization. Nature Cell Biol. 1, 136–143 (1999).

    CAS  PubMed  Google Scholar 

  79. Sagot, I., Klee, S. K. & Pellman, D. Yeast formins regulate cell polarity by controlling the assembly of actin cables. Nature Cell Biol. 4, 42–50 (2002). Together with reference 77, this paper showed that the FH2 domain has a crucial role in actin assembly in vivo , setting the stage for the biochemical studies on formin activities that followed.

    CAS  PubMed  Google Scholar 

  80. Sarmiento, C. et al. WASP family members and formin proteins coordinate regulation of cell protrusions in carcinoma cells. J. Cell Biol. 180, 1245–1260 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Tominaga, T. et al. Diaphanous-related formins bridge Rho GTPase and Src tyrosine kinase signaling. Mol. Cell 5, 13–25 (2000).

    CAS  PubMed  Google Scholar 

  82. Alberts, A. S. Identification of a carboxyl-terminal diaphanous-related formin homology protein autoregulatory domain. J. Biol. Chem. 276, 2824–2830 (2001). This study provided the first detailed evidence for autoinhibition by formins and defined the autoregulatory function of the DAD.

    CAS  PubMed  Google Scholar 

  83. Li, F. & Higgs, H. N. Dissecting requirements for auto-inhibition of actin nucleation by the formin, mDia1. J. Biol. Chem. 280, 6986–6992 (2005).

    CAS  PubMed  Google Scholar 

  84. Seth, A., Otomo, C. & Rosen, M. K. Autoinhibition regulates cellular localization and actin assembly activity of the diaphanous-related formins FRLα and mDia1. J. Cell Biol. 174, 701–713 (2006). This study showed that autoinhibitory interactions between the N- and C-terminal halves of the formins FMNL1 and mDia1 regulate their localization to the cell cortex, and that Rho proteins, along with other unidentified factors, facilitate formin cortical recruitment.

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Lu, J. et al. Structure of the FH2 domain of Daam1: implications for formin regulation of actin assembly. J. Mol. Biol. 369, 1258–1269 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Yamashita, M. et al. Crystal structure of human DAAM1 formin homology 2 domain. Genes Cells 12, 1255–1265 (2007).

    CAS  PubMed  Google Scholar 

  87. Chhabra, E. S., Ramabhadran, V., Gerber, S. A. & Higgs, H. N. INF2 is an endoplasmic reticulum-associated formin protein. J. Cell Sci. 122, 1430–1440 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Eisenmann, K. M. et al. Dia-interacting protein modulates formin-mediated actin assembly at the cell cortex. Curr. Biol. 17, 579–591 (2007).

    CAS  PubMed  Google Scholar 

  89. Chesarone, M., Gould, C. J., Moseley, J. B. & Goode, B. L. Displacement of formins from growing barbed ends by Bud14 is critical for actin cable architecture and function. Dev. Cell 16, 292–302 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Heasman, S. J. & Ridley, A. J. Mammalian Rho GTPases: new insights into their functions from in vivo studies. Nature Rev. Mol. Cell Biol. 9, 690–701 (2008).

    CAS  Google Scholar 

  91. Imamura, H. et al. Bni1p and Bnr1p: downstream targets of the Rho family small G-proteins which interact with profilin and regulate actin cytoskeleton in Saccharomyces cerevisiae. EMBO J. 16, 2745–2755 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Dong, Y., Pruyne, D. & Bretscher, A. Formin-dependent actin assembly is regulated by distinct modes of Rho signaling in yeast. J. Cell Biol. 161, 1081–1092 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Brandt, D. T. et al. Dia1 and IQGAP1 interact in cell migration and phagocytic cup formation. J. Cell Biol. 178, 193–200 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Wang, J., Neo, S. P. & Cai, M. Regulation of the yeast formin Bni1p by the actin-regulating kinase Prk1p. Traffic 10, 528–535 (2009).

    CAS  PubMed  Google Scholar 

  95. Matheos, D., Metodiev, M., Muller, E., Stone, D. & Rose, M. D. Pheromone-induced polarization is dependent on the Fus3p MAPK acting through the formin Bni1p. J. Cell Biol. 165, 99–109 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Tolliday, N., VerPlank, L. & Li, R. Rho1 directs formin-mediated actin ring assembly during budding yeast cytokinesis. Curr. Biol. 12, 1864–1870 (2002).

    CAS  PubMed  Google Scholar 

  97. Yoshida, S. et al. Polo-like kinase Cdc5 controls the local activation of Rho1 to promote cytokinesis. Science 313, 108–111 (2006).

    CAS  PubMed  Google Scholar 

  98. Das, M. et al. Regulation of cell diameter, For3p localization, and cell symmetry by fission yeast Rho-GAP Rga4p. Mol. Biol. Cell 18, 2090–2101 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Copeland, S. J. et al. The diaphanous inhibitory domain/diaphanous autoregulatory domain interaction is able to mediate heterodimerization between mDia1 and mDia2. J. Biol. Chem. 282, 30120–30130 (2007).

    CAS  PubMed  Google Scholar 

  100. Carramusa, L., Ballestrem, C., Zilberman, Y. & Bershadsky, A. D. Mammalian diaphanous-related formin Dia1 controls the organization of E-cadherin-mediated cell-cell junctions. J. Cell Sci. 120, 3870–3882 (2007).

    CAS  PubMed  Google Scholar 

  101. Petersen, J., Nielsen, O., Egel, R. & Hagan, I. M. FH3, a domain found in formins, targets the fission yeast formin Fus1 to the projection tip during conjugation. J. Cell Biol. 141, 1217–1228 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Kikyo, M. et al. An FH domain-containing Bnr1p is a multifunctional protein interacting with a variety of cytoskeletal proteins in Saccharomyces cerevisiae. Oncogene 18, 7046–7054 (1999).

    CAS  PubMed  Google Scholar 

  103. Fujiwara, T. et al. Rho1p–Bni1p–Spa2p interactions: implication in localization of Bni1p at the bud site and regulation of the actin cytoskeleton in Saccharomyces cerevisiae. Mol. Biol. Cell 9, 1221–1233 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Martin, S. G., McDonald, W. H., Yates, J. R., & Chang, F. Tea4p links microtubule plus ends with the formin for3p in the establishment of cell polarity. Dev. Cell 8, 479–491 (2005).

    CAS  PubMed  Google Scholar 

  105. Ryu, J. R., Echarri, A., Li, R. & Pendergast, A. M. Regulation of cell-cell adhesion by Abi/Diaphanous complexes. Mol. Cell. Biol. 29, 1735–1748 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Kobielak, A., Pasolli, H. A. & Fuchs, E. Mammalian formin-1 participates in adherens junctions and polymerization of linear actin cables. Nature Cell Biol. 6, 21–30 (2004).

    CAS  PubMed  Google Scholar 

  107. Goley, E. D. & Welch, M. D. The ARP2/3 complex: an actin nucleator comes of age. Nature Rev. Mol. Cell Biol. 7, 713–726 (2006).

    CAS  Google Scholar 

  108. Moseley, J. B., Maiti, S. & Goode, B. L. Formin proteins: purification and measurement of effects on actin assembly. Methods Enzymol. 406, 215–234 (2006).

    CAS  PubMed  Google Scholar 

  109. Buttery, S. M., Yoshida, S. & Pellman, D. Yeast formins Bni1 and Bnr1 utilize different modes of cortical interaction during the assembly of actin cables. Mol. Biol. Cell 18, 1826–1838 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  110. Martin, S. G. & Chang, F. Dynamics of the formin For3p in actin cable assembly. Curr. Biol. 16, 1161–1170 (2006). Together with reference 109, this study used high resolution live-cell imaging to show that some formins can be transiently recruited from the cytoplasm to the cell cortex, where they assemble actin and are then released from the cortex and incorporated into actin networks, whereas other formins are stably tethered to cortical sites of actin assembly.

    CAS  PubMed  Google Scholar 

  111. Stradal, T. E. & Scita, G. Protein complexes regulating Arp2/3-mediated actin assembly. Curr. Opin. Cell Biol. 18, 4–10 (2006).

    CAS  PubMed  Google Scholar 

  112. Chan, D. C., Bedford, M. T. & Leder, P. Formin binding proteins bear WWP/WW domains that bind proline-rich peptides and functionally resemble SH3 domains. EMBO J. 15, 1045–1054 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Aspenstrom, P., Richnau, N. & Johansson, A. S. The diaphanous-related formin DAAM1 collaborates with the Rho GTPases RhoA and Cdc42, CIP4 and Src in regulating cell morphogenesis and actin dynamics. Exp. Cell Res. 312, 2180–2194 (2006).

    PubMed  Google Scholar 

  114. Uetz, P., Fumagalli, S., James, D. & Zeller, R. Molecular interaction between limb deformity proteins (formins) and Src family kinases. J. Biol. Chem. 271, 33525–33530 (1996).

    CAS  PubMed  Google Scholar 

  115. Gasman, S., Kalaidzidis, Y. & Zerial, M. RhoD regulates endosome dynamics through Diaphanous-related Formin and Src tyrosine kinase. Nature Cell Biol. 5, 195–204 (2003).

    CAS  PubMed  Google Scholar 

  116. 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. 271, 626–629 (2000).

    CAS  PubMed  Google Scholar 

  117. Scita, G., Confalonieri, S., Lappalainen, P. & Suetsugu, S. IRSp53: crossing the road of membrane and actin dynamics in the formation of membrane protrusions. Trends Cell Biol. 18, 52–60 (2008).

    CAS  PubMed  Google Scholar 

  118. Cramer, L. P., Siebert, M. & Mitchison, T. J. Identification of novel graded polarity actin filament bundles in locomoting heart fibroblasts: implications for the generation of motile force. J. Cell Biol. 136, 1287–1305 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  119. Kamasaki, T., Arai, R., Osumi, M. & Mabuchi, I. Directionality of F-actin cables changes during the fission yeast cell cycle. Nature Cell Biol. 7, 916–917 (2005).

    CAS  PubMed  Google Scholar 

  120. Kamasaki, T., Osumi, M. & Mabuchi, I. Three-dimensional arrangement of F-actin in the contractile ring of fission yeast. J. Cell Biol. 178, 765–771 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  121. Yang, H. C., Simon, V., Swayne, T. C. & Pon, L. Visualization of mitochondrial movement in yeast. Methods Cell Biol. 65, 333–351 (2001).

    CAS  PubMed  Google Scholar 

  122. Skau, C. T., Neidt, E. M. & Kovar, D. R. Role of tropomyosin in formin-mediated contractile ring assembly in fission yeast. Mol. Biol. Cell 20, 2160–2173 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  123. Deward, A. D. & Alberts, A. S. Ubiquitin-mediated degradation of the formin mDia2 upon completion of cell division. J. Biol. Chem. 284, 20061–20069 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  124. Favaro, P. M. et al. Human leukocyte formin: a novel protein expressed in lymphoid malignancies and associated with Akt. Biochem. Biophys. Res. Commun. 311, 365–371 (2003).

    CAS  PubMed  Google Scholar 

  125. Favaro, P. M. et al. High expression of FMNL1 protein in T non-Hodgkin's lymphomas. Leuk. Res. 30, 735–738 (2006).

    CAS  PubMed  Google Scholar 

  126. Zhu, X. L., Liang, L. & Ding, Y. Q. Overexpression of FMNL2 is closely related to metastasis of colorectal cancer. Int. J. Colorectal Dis. 23, 1041–1047 (2008).

    PubMed  Google Scholar 

  127. Lizarraga, F. et al. Diaphanous-related formins are required for invadopodia formation and invasion of breast tumor cells. Cancer Res. 69, 2792–2800 (2009).

    CAS  PubMed  Google Scholar 

  128. Sahai, E. & Marshall, C. J. RHO-GTPases and cancer. Nature Rev. Cancer 2, 133–142 (2002).

    Google Scholar 

  129. Carreira, S. et al. Mitf regulation of Dia1 controls melanoma proliferation and invasiveness. Genes Dev. 20, 3426–3439 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  130. Eisenmann, K. M. et al. T cell responses in mammalian diaphanous-related formin mDia1 knock-out mice. J. Biol. Chem. 282, 25152–25158 (2007).

    CAS  PubMed  Google Scholar 

  131. Jones, S. et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 321, 1801–1806 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  132. Parsons, D. W. et al. An integrated genomic analysis of human glioblastoma multiforme. Science 321, 1807–1812 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  133. Schuster, I. G. et al. Allorestricted T cells with specificity for the FMNL1-derived peptide PP2 have potent antitumor activity against hematologic and other malignancies. Blood 110, 2931–2939 (2007).

    CAS  PubMed  Google Scholar 

  134. Peng, J. et al. Myeloproliferative defects following targeting of the Drf1 gene encoding the mammalian diaphanous related formin mDia1. Cancer Res. 67, 7565–7571 (2007).

    CAS  PubMed  Google Scholar 

  135. Gomez, T. S. et al. Formins regulate the actin-related protein 2/3 complex-independent polarization of the centrosome to the immunological synapse. Immunity 26, 177–190 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  136. Colucci-Guyon, E. et al. A role for mammalian diaphanous-related formins in complement receptor (CR3)-mediated phagocytosis in macrophages. Curr. Biol. 15, 2007–2012 (2005).

    CAS  PubMed  Google Scholar 

  137. Leader, B. et al. Formin-2, polyploidy, hypofertility and positioning of the meiotic spindle in mouse oocytes. Nature Cell Biol. 4, 921–928 (2002).

    CAS  PubMed  Google Scholar 

  138. Dumont, J. et al. Formin-2 is required for spindle migration and for the late steps of cytokinesis in mouse oocytes. Dev. Biol. 301, 254–265 (2007).

    CAS  PubMed  Google Scholar 

  139. Castrillon, D. H. & Wasserman, S. A. Diaphanous is required for cytokinesis in Drosophila and shares domains of similarity with the products of the limb deformity gene. Development 120, 3367–3377 (1994). This pioneering study first defined the formin gene family and was the first to show that formins play crucial parts in cytokinesis.

    CAS  PubMed  Google Scholar 

  140. Magie, C. R., Meyer, M. R., Gorsuch, M. S. & Parkhurst, S. M. Mutations in the Rho1 small GTPase disrupt morphogenesis and segmentation during early Drosophila development. Development 126, 5353–5364 (1999).

    CAS  PubMed  Google Scholar 

  141. Afshar, K., Stuart, B. & Wasserman, S. A. Functional analysis of the Drosophila diaphanous FH protein in early embryonic development. Development 127, 1887–1897 (2000).

    CAS  PubMed  Google Scholar 

  142. Grosshans, J. et al. RhoGEF2 and the formin Dia control the formation of the furrow canal by directed actin assembly during Drosophila cellularisation. Development 132, 1009–1020 (2005).

    CAS  PubMed  Google Scholar 

  143. Zhou, F., Leder, P., Zuniga, A. & Dettenhofer, M. Formin1 disruption confers oligodactylism and alters Bmp signaling. Hum. Mol. Genet. 18, 2472–2482 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  144. Bione, S. 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. 62, 533–541 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  145. Lynch, E. D. et al. Nonsyndromic deafness DFNA1 associated with mutation of a human homolog of the Drosophila gene diaphanous. Science 278, 1315–1318 (1997).

    CAS  PubMed  Google Scholar 

  146. Schirenbeck, A., Bretschneider, T., Arasada, R., Schleicher, M. & Faix, J. The Diaphanous-related formin dDia2 is required for the formation and maintenance of filopodia. Nature Cell Biol. 7, 619–625 (2005).

    CAS  PubMed  Google Scholar 

  147. Yang, C. et al. Novel roles of formin mDia2 in lamellipodia and filopodia formation in motile cells. PLoS Biol. 5, e317 (2007).

    PubMed  PubMed Central  Google Scholar 

  148. Otomo, T. & Rosen, M. K. Structure and function of Formin homology 2 domain. Tanpakushitsu Kakusan Koso 50, 1088–1093 (2005).

    CAS  PubMed  Google Scholar 

  149. Amberg, D. C., Zahner, J. E., Mulholland, J. W., Pringle, J. R. & Botstein, D. Aip3p/Bud6p, a yeast actin-interacting protein that is involved in morphogenesis and the selection of bipolar budding sites. Mol. Biol. Cell 8, 729–753 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  150. Qi, M. & Elion, E. A. Formin-induced actin cables are required for polarized recruitment of the Ste5 scaffold and high level activation of MAPK Fus3. J. Cell Sci. 118, 2837–2848 (2005).

    CAS  PubMed  Google Scholar 

  151. Ozaki-Kuroda, K. et al. Dynamic localization and function of Bni1p at the sites of directed growth in Saccharomyces cerevisiae. Mol. Cell Biol. 21, 827–839 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  152. Carnahan, R. H. & Gould, K. L. The PCH family protein, Cdc15p, recruits two F-actin nucleation pathways to coordinate cytokinetic actin ring formation in Schizosaccharomyces pombe. J. Cell Biol. 162, 851–862 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  153. Feierbach, B., Verde, F. & Chang, F. Regulation of a formin complex by the microtubule plus end protein Tea1p. J. Cell Biol. 165, 697–707 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  154. Goulimari, P. et al. Gα12/13 is essential for directed cell migration and localized Rho–Dia1 function. J. Biol. Chem. 280, 42242–42251 (2005).

    CAS  PubMed  Google Scholar 

  155. 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. 118, 2661–2670 (2005).

    CAS  PubMed  Google Scholar 

  156. Pellegrin, S. & Mellor, H. The Rho family GTPase Rif induces filopodia through mDia2. Curr. Biol. 15, 129–133 (2005).

    CAS  PubMed  Google Scholar 

  157. Nakaya, M. A. et al. Identification and comparative expression analyses of Daam genes in mouse and Xenopus. Gene Expr Patterns 5, 97–105 (2004).

    CAS  PubMed  Google Scholar 

  158. Matusek, T. et al. The Drosophila formin DAAM regulates the tracheal cuticle pattern through organizing the actin cytoskeleton. Development 133, 957–966 (2006).

    CAS  PubMed  Google Scholar 

  159. Matusek, T. et al. Formin proteins of the DAAM subfamily play a role during axon growth. J. Neurosci. 28, 13310–13319 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  160. Yamashita, T. et al. Identification and characterization of a novel Delphilin variant with an alternative N-terminus. Brain Res. Mol. Brain Res. 141, 83–94 (2005).

    CAS  PubMed  Google Scholar 

  161. Hotulainen, P. & Lappalainen, P. Stress fibers are generated by two distinct actin assembly mechanisms in motile cells. J. Cell Biol. 173, 383–394 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  162. Koka, S., Minick, G. T., Zhou, Y., Westendorf, J. J. & Boehm, M. B. Src regulates the activity of the mammalian formin protein FHOD1. Biochem. Biophys. Res. Commun. 336, 1285–1291 (2005).

    CAS  PubMed  Google Scholar 

  163. Gasteier, J. E. et al. FHOD1 coordinates actin filament and microtubule alignment to mediate cell elongation. Exp. Cell Res. 306, 192–202 (2005).

    CAS  PubMed  Google Scholar 

  164. Schulte, A. et al. The human formin FHOD1 contains a bipartite structure of FH3 and GTPase-binding domains required for activation. Structure 16, 1313–1323 (2008).

    CAS  PubMed  Google Scholar 

  165. Bosch, M. et al. Analysis of the function of Spire in actin assembly and its synergy with formin and profilin. Mol. Cell 28, 555–568 (2007).

    CAS  PubMed  Google Scholar 

  166. Dettenhofer, M., Zhou, F. & Leder, P. Formin 1-isoform IV deficient cells exhibit defects in cell spreading and focal adhesion formation. PLoS ONE 3, e2497 (2008).

    PubMed  PubMed Central  Google Scholar 

  167. Schuh, M. & Ellenberg, J. A new model for asymmetric spindle positioning in mouse oocytes. Curr. Biol. 18, 1986–1992 (2008).

    CAS  PubMed  Google Scholar 

  168. Li, H., Guo, F., Rubinstein, B. & Li, R. Actin-driven chromosomal motility leads to symmetry breaking in mammalian meiotic oocytes. Nature Cell Biol. 10, 1301–1308 (2008).

    CAS  PubMed  Google Scholar 

  169. Yayoshi-Yamamoto, S., Taniuchi, I. & Watanabe, T. FRL, a novel formin-related protein, binds to Rac and regulates cell motility and survival of macrophages. Mol. Cell. Biol. 20, 6872–6881 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We are grateful to J. Moseley, I. Sagot and members of the Goode laboratory for helpful discussions and editing the manuscript, and A. Alberts for sharing information before publication. We apologize to colleagues whose work was not highlighted owing to space limitations. This work was supported in part by grants from the National Institutes of Health to B.G. (GM63691 and GM083137).

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Glossary

Polyproline tract

A short protein motif, found in many actin regulatory scaffold proteins, that typically contains five or more tandem proline residues and binds profilin or SH3 domains.

Barbed end

The rapidly growing end of an actin filament, so-called because of the arrowhead pattern created when myosin binds. The slowly growing end is called the pointed end.

Microtubule plus end tracking protein

One of a group of proteins that are enriched at the fast growing (plus) ends of microtubules and that influence microtubule dynamics and/or link microtubule plus ends to other cellular structures.

Coiled-coil domain

A structural domain that can mediate protein oligomerization. Coiled coils are helices that are assembled from repeat sequences of seven amino acids (heptads) and twist around each other to form a supercoil.

Armadillo repeat

A folded helical structure encoded by a conserved sequence that was first identified in the D. melanogaster protein Armadillo. This domain is conserved in animals and higher plants and is found in various signalling and cytoskeletal proteins.

PDZ domain

(Postsynaptic-density protein of 95 kDa, Discs large and Zona occludens-1 domain). A protein-interaction domain that often occurs in scaffolding proteins and is named after the founding members of the family.

PTEN domain

(Phosphatase and tensin domain). A conserved lipid protein phosphatase domain that has been extensively characterized in the tumour suppressor protein PTEN. Many PTEN domain-containing proteins regulate cytoskeletal organization.

Total internal reflection fluorescence microscopy

A microscopy technique that enables the real-time visualization of fluorescently labelled molecules in a thin region of a specimen, greatly reducing background, and that has enabled actin dynamics to be studied at the single filament level.

F-actin

(Filamentous actin). A flexible, helical polymer of globular actin (G-actin) subunits, with a diameter of 5–9 nm.

Capping protein

One of a group of ubiquitously expressed proteins that are found in eukaryotic cells and show high affinity for the barbed ends of actin filaments, thereby antagonizing filament growth.

ENA/VASP

(Enabled/vasodilator-stimulated phosphoprotein). A member of a family of actin-binding proteins that are required for many cellular processes, including motility. Similar to formins, ENA/VASP proteins associate with the barbed ends of actin filaments and protect growing filaments from capping proteins, although they appear to use a distinct mechanism.

Kinetochore

A large multiprotein complex that assembles onto the centromeric DNA of chromosomes and links the chromosome to microtubule plus ends in the mitotic spindle. It plays an instrumental role in chromosome segregation during mitosis.

Microtubule array

A spatial arrangement of microtubule polymers harnessed to cellular tasks that include mitosis, intracellular transport and directional cell movement.

Amphipathic helix

A helical structure that consists of hydrophobic non-polar residues on one side and hydrophilic polar residues on the other side.

Rho GTPase

One of a conserved family of small enzymes that converts GTP to GDP and acts as a 'molecular switch' that is active in the GTP-bound form and inactive in the GDP-bound form. Active Rho proteins bind to effectors, such as formins, to trigger cytoskeletal remodelling.

Farnesylation

A post-translational modification in which a farnesyl group (a hydrophobic group of three isoprene units) is conjugated to proteins, such as Ras GTPases, that contain a C-terminal CAAX motif. Farnesylation promotes insertion of the modified proteins into lipid bilayers.

Phagocytic cup

An actin-rich, cup-like extension of the peripheral membrane that partially encircles foreign particles or bacteria during the early stages of the phagocytic process.

WAVE complex

(WASP-family verprolin-homologous protein complex). A complex of five proteins that regulates Arp2/3 complex-mediated actin assembly. The defining member of this complex, WAVE, is related to WASP and directly stimulates the Arp2/3 complex to nucleate actin assembly, while other components of the complex regulate WAVE.

Adherens junction

A cell–cell adhesion complex that contains classical cadherins and catenins, which are attached to cytoplasmic actin filaments.

α-catenin

A central component of adherens junctions that links cell adhesion molecules, such as cadherin, to actin filaments.

Tropomyosin

One of a conserved family of actin binding proteins that bind to the sides of actin filaments, stabilizing actin, and in some cases binds to formins to promote actin assembly.

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Chesarone, M., DuPage, A. & Goode, B. Unleashing formins to remodel the actin and microtubule cytoskeletons. Nat Rev Mol Cell Biol 11, 62–74 (2010). https://doi.org/10.1038/nrm2816

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