Biochemistry (Moscow)

, Volume 79, Issue 9, pp 917–927 | Cite as

Intracellular transport based on actin polymerization



In addition to the intracellular transport of particles (cargo) along microtubules, there are in the cell two actin-based transport systems. In the actomyosin system the transport is driven by myosin, which moves the cargo along actin microfilaments. This transport requires the hydrolysis of ATP in the myosin molecule motor domain that induces conformational changes in the molecule resulting in the myosin movement along the actin filament. The other actin-based transport system of the cell does not involve myosin or other motor proteins. This system is based on a unidirectional actin polymerization, which depends on ATP hydrolysis in actin polymers and is initiated by proteins bound to the surface of transported particles. Obligatory components of the actin-based transport are proteins of the WASP/Scar family and a complex of Arp2/3 proteins. Moreover, the actin-based systems often contain dynamin and cortactin. It is known that a system of actin filaments formed on the surface of particles, the so-called “comet-like tail”, is responsible for intracellular movements of pathogenic bacteria, micropinocytotic vesicles, clathrin-coated vesicles, and phagosomes. This movement is reproduced in a cell-free system containing extract of Xenopus oocytes. The formation of a comet-like structure capable of transporting vesicles from the plasma membrane into the cell depth has been studied in detail by high performance electron microscopy combined with electron tomography. A similar mechanism provides the movement of vesicles containing membrane rafts enriched with sphingolipids and cholesterol, changes in position of the nuclear spindle at meiosis, and other processes. This review will consider current ideas about actin polymerization and its regulation by actin-binding proteins and show how these mechanisms are realized in the intracellular actin-based vesicular transport system.

Key words

cytoskeleton actin Arp2/3 dynamin intracellular vesicles “comet-like tails” 


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  1. 1.
    Langford, G. M. (1995) Actin- and microtubule-dependent organelle motors: interrelationships between the two motility systems, Curr. Opin. Cell Biol., 7, 82–88.PubMedCrossRefGoogle Scholar
  2. 2.
    Maravillas-Montero, J., and Santos-Argumedo, L. (2013) The myosin family: unconventional roles of actin-dependent molecular motors in immune cells, J. Leukocyte Biol., 91, 35–45.CrossRefGoogle Scholar
  3. 3.
    Hammer, J. A., 3rd, and Sellers, J. R. (2012) Walking to work: roles for class V myosins as cargo transporters, Nat. Rev. Mol. Cell. Biol., 13, 13–26.Google Scholar
  4. 4.
    Mehta, A. D., Rock, R. S., Rief, M., Spudich, J. A., Mooseker, M. S., and Cheney, R. E. (1999) Myosin-V is a processive actin-based motor, Nature, 400, 590–593.PubMedCrossRefGoogle Scholar
  5. 5.
    Wollert, T. D., Weiss, G., Gerdes, H.-H., and Kuznetsov, S. A. (2002) Activation of myosin V-based motility and F-actin-dependent network formation of endoplasmic reticulum during mitosis, J. Cell Biol., 150, 571–577.CrossRefGoogle Scholar
  6. 6.
    Kapitein, L. C., van Bergeijk, P., Lipka, J., Keijzer, N., Wulf, P. S., Katrukha, E. A., Akhmanova, A., and Hoogenraad, C. C. (2013) Myosin-V opposes microtubule-based cargo transport and drives directional motility on cortical actin, Curr. Biol., 23, 828–834.PubMedCrossRefGoogle Scholar
  7. 7.
    Von Delius, M., and Leigh, D. A. (2011) Walking molecules, Chem. Soc. Rev., 40, 3656–3676.CrossRefGoogle Scholar
  8. 8.
    Van den Berg, R., and Hoogenraad, C. C. (2012) Molecular motors in cargo trafficking and synapse assembly, Adv. Exp. Med. Biol., 970, 173–196.PubMedCrossRefGoogle Scholar
  9. 9.
    Ali, M. Y., Lu, H., Bookwalter, C. S., Warshaw, D. M., and Trybus, K. M. (2008) Myosin V and kinesin act as tethers to enhance each others’ processivity, Proc. Natl. Acad. Sci. USA, 105, 4691–4696.PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    Ross, J. L., Ali, M. Y., and Warshaw, D. M. (2008) Cargo transport: molecular motors navigate a complex cytoskeleton, Curr. Opin. Cell Biol., 20, 41–47.PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Schroeder, H. W., III, Mitchell, C., Shuman, H., Holzbaur, E. L., and Goldman, Y. E. (2010) Motor number controls cargo switching at actin-microtubule intersections in vitro, Curr. Biol., 20, 687–696.PubMedCrossRefGoogle Scholar
  12. 12.
    Le Clainche, C., and Carlier, M.-F. (2008) Regulation of actin assembly associated with protrusion and adhesion in cell migration, Physiol. Rev., 88, 489–513.PubMedCrossRefGoogle Scholar
  13. 13.
    Schafer, D. A., Weed, S. A., Binns, D., Karginov, A. V., Parsons, J. T., and Cooper, J. A. (2002) Dynamin 2 and cortactin regulate actin assembly and filament organization, Curr. Biol., 12, 1852–1857.PubMedCrossRefGoogle Scholar
  14. 14.
    Merrifield, C. J., Moss, S. E., Ballestrem, C., Imhof, B. A., Giese, G., Wunderlich, I., and Almers, W. (1999) Endocytic vesicles move at the tips of actin tails in cultured mast cells, Nat. Cell Biol., 1, 72–74.PubMedCrossRefGoogle Scholar
  15. 15.
    Orth, J. D., Krueger, E. W., Cao, H., and McNiven, M. A. (2002) The large GTPase dynamin regulates actin comet formation and movement in living cells, Proc. Natl. Acad. Sci. USA, 99, 167–172.PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Merrifield, C. J., Feldman, M. E., Wan, L., and Almers, W. (2002) Imaging actin and dynamin recruitment during invagination of single clathrin-coated pits, Nature Cell Biol., 4, 691–698.PubMedCrossRefGoogle Scholar
  17. 17.
    Taunton, J., Rowning, B. A., Coughlin, M. L., Wu, M., Moon, R. T., Mitchison, T. J., and Larabell, C. A. (2000) Actin-dependent propulsion of endosomes and lysosomes by recruitment of N-WASP, J. Cell. Biol., 148, 519–530.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Rozelle, A. L., Machesky, L. M., Yamamoto, M., Driessens, M. H., Insall, R. H., Roth, M. G., Luby-Phelps, K., Marriott, G., Hall, A., and Yin, H. L. (2000) Phosphatidylinositol 4,5-bisphosphate induces actin-based movement of raft enriched vesicles through WASP-Arp2/3, Curr. Biol., 10, 311–320.PubMedCrossRefGoogle Scholar
  19. 19.
    Bezanilla, M., and Wadsworth, P. (2008) Spindle positioning: actin mediates pushing and pulling, Curr. Biol., 19, R168–R169.CrossRefGoogle Scholar
  20. 20.
    Fabritius, A. S., Ellefson, M. L., and McNally, J. (2011) Nuclear and spindle positioning during oocyte meiosis, Curr. Opin. Cell Biol., 23, 78–84.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Li, R., and Albertini, D. F. (2013) The road to maturation: somatic cell interaction and self-organization of the mammalian oocyte, Nat. Rev. Mol. Cell. Biol., 14, 141–152.PubMedCrossRefGoogle Scholar
  22. 22.
    Kabsch, W., Mannherz, H. G., Suck, D., Pai, E. F., and Holmes, K. C. (1990) Atomic structure of the actin-DNase I complex, Nature, 347, 37–44.PubMedCrossRefGoogle Scholar
  23. 23.
    Hanson, J., and Lowy, J. (1963) The structure of F-actin and of actin filaments isolated from muscle, J. Mol. Biol., 6, 46–60.CrossRefGoogle Scholar
  24. 24.
    Dominguez, R., and Holmes, K. C. (2011) Actin structure and function, Annu. Rev. Biophys., 40, 169–186.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Woodrum, D. T., Rich, S. A., and Pollard, T. D. (1975) Evidence for biased bidirectional polymerization of actin filaments using heavy meromyosin prepared by an improved method, J. Cell Biol., 67, 231–237.PubMedCrossRefGoogle Scholar
  26. 26.
    Schuler, H. (2001) ATPase activity and conformational changes in the regulation of actin, Biochim. Biophys. Acta, 1549, 137–147.PubMedCrossRefGoogle Scholar
  27. 27.
    Pollard, T. D., and Borisy, G. G. (2003) Cellular motility driven by assembly and disassembly of actin filaments, Cell, 112, 453–465.PubMedCrossRefGoogle Scholar
  28. 28.
    Pantaloni, D., Le Clainche, C., and Carlier, M.-F. (2001) Mechanism of actin-based motility, Science, 292, 1502–1506.PubMedCrossRefGoogle Scholar
  29. 29.
    Chhabra, E. S., and Higgs, H. N. (2007) The many faces of actin: matching assembly factors with cellular structures, Nat. Cell Biol., 9, 1110–1121.PubMedCrossRefGoogle Scholar
  30. 30.
    Domingues, R. (2009) Actin filament nucleation and elongation factors — structure-function relationships, Crit. Rev. Biochem. Mol. Biol., 44, 351–366.CrossRefGoogle Scholar
  31. 31.
    Mullins, R. D., Heuser, J. A., and Pollard, T. D. (1998) The interaction of Arp2/3 complex with actin: nucleation, high affinity pointed end capping, and formation of branching networks of filaments, Proc. Natl. Acad. Sci. USA, 95, 6181–6186.PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Svitkina, T. M., Verkhovsky, A. B., and Borisy, G. G. (1995) Improved procedures for electron microscopic visualization of the cytoskeleton of cultured cells, J. Struct. Biol., 115, 290–303.PubMedCrossRefGoogle Scholar
  33. 33.
    Cossart, P., and Sansonetti, P. J. (2004) Bacterial invasion: the paradigms of enteroinvasive pathogens, Science, 304, 242–248.PubMedCrossRefGoogle Scholar
  34. 34.
    Theriot, J. A., Mitchison, T. J., Tilney, L. G., and Portnoy, D. A. (1992) The rate of actin-based motility of intracellular Listeria monocytogenes equals the rate of actin polymerization, Nature, 357, 257–260.PubMedCrossRefGoogle Scholar
  35. 35.
    Tilney, L. G., Connelly, P. S., and Portnoy, D. A. (1990) Actin filament nucleation by the bacterial pathogen, Listeria monocytogenes, J. Cell Biol., 111, 2979–2988.PubMedCrossRefGoogle Scholar
  36. 36.
    Mounier, J., Ryter, A., Coquis-Rondon, M., and Sansonetti, P. J. (1989) Intracellular and cell-to-cell spread of Listeria monocytogenes involves interaction with F-actin in the enterocyte-like cell line Caco-2, Infect. Immun., 58, 1048–1058.Google Scholar
  37. 37.
    Gouin, E., Gantelet, H., Egile, C., Lasa, I., Ohayon, H., Villiers, V., Gounon, P., Sansonetti, P. J., and Cossart, P. (1999) A comparative study of the actin-based motilities of the pathogenic bacteria Listeria monocytogenes, Shigella flexneri and Rickettsia conorii, J. Cell Sci., 112, 1697–1708.PubMedGoogle Scholar
  38. 38.
    Gouin, E., Welch, M. D., and Cossart, P. (2005) Actin-based motility of intracellular pathogens, Curr. Opin. Microbiol., 8, 35–45.PubMedCrossRefGoogle Scholar
  39. 39.
    Pistor, S., Chakraborty, T., Niebuhr, K., Domann, E., and Wehland, J. (1994) The ActA protein of Listeria monocytogenes acts as a nucleator inducing reorganization of the actin cytoskeleton, EMBO J., 13, 758–763.PubMedPubMedCentralGoogle Scholar
  40. 40.
    Kocks, C., Marchand, J. B., Gouin, E., d’Hauteville, H., Sansonetti, P. J., Carlier, M. F., and Cossart, P. (1995) The unrelated surface proteins ActA of Listeria monocytogenes and IcsA of Shigella flexneri are sufficient to confer actin-based motility on Listeria innocua and Escherichia coli, respectively, Mol. Microbiol., 18, 413–423.PubMedCrossRefGoogle Scholar
  41. 41.
    Bernardini, M. L., Mounier, J., Hauteville, H. L., Coquis-Ronton, M., and Sansonetti, P. J. (1989) Identification of IcsA, a plasmid locus of Shigella flexneri that governs bacterial intra- and intercellular spread through interaction with F-actin, Proc. Nat. Acad. Sci. USA, 86, 3867–3871.PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Smith, G. A., Portnoy, D. A., and Theriot, J. A. (1995) Asymmetric distribution of the Listeria monocytogenes ActA protein is required and sufficient to direct actin-based motility, Mol. Microbiol., 17, 945–951.PubMedCrossRefGoogle Scholar
  43. 43.
    Goldberg, M. B., Barzu, O., Parsot, C., and Sansonetti, P. J. (1993) Unipolar localization and ATPase activity of Ics A, a Shigella flexneri protein involved in intracellular movement, J. Bacteriol., 175, 2189–2196.PubMedPubMedCentralGoogle Scholar
  44. 44.
    Campellone, K. G., and Welch, M. D. (2010) A nucleator arms race: cellular control of actin assembly, Nat. Rev. Mol. Cell Biol., 11, 237–251.PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Suzuki, T., Miki, H., Takenawa, T., and Sasakawa, C. (1998) Neural Wiskott-Aldrich syndrome protein is implicated in the actin-based motility of Shigella flexneri, EMBO J., 17, 2767–2776.PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Egile, C., Loisel, T. P., Laurent, V., Pantaloni, D., Sansonetti, P. J., and Carlier, M.-F. (1999) Activation of the CDC42 effector N-WASP by the Shigella flexneri IcsA protein promotes actin nucleation by Arp2/3 complex and bacterial actin-based motility, J. Cell Biol., 146, 1319–1322.PubMedCrossRefPubMedCentralGoogle Scholar
  47. 47.
    Mogilner, A., and Oster, G. (1996) Cell motility driven by actin polymerization, Biophys. J., 71, 3030–3045.PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    Loisel, T. P., Boujemaa, R., Pantaloni, D., and Carlier, M. F. (1999) Reconstitution of actin-based motility of Listeria and Shigella using pure proteins, Nature, 401, 613–616.PubMedCrossRefGoogle Scholar
  49. 49.
    Machesky, L. M., and Cooper, J. A. (1999) Bare bones of the cytoskeleton, Nature, 401, 542–543.PubMedCrossRefGoogle Scholar
  50. 50.
    Bravo-Cordero, J. J., Magalhaes, M. A., Eddy, R. J., Hodgson, L., and Condeelis, J. (2013) Functions of cofilin in cell locomotion and invasion, Nat. Rev. Mol. Cell. Biol., 14, 405–415.PubMedCrossRefGoogle Scholar
  51. 51.
    Krishnan, K., and Moens, P. D. J. (2009) Structure and functions of profilins, Biophys. Rev., 1, 71–81.CrossRefGoogle Scholar
  52. 52.
    Borisi, G. G., and Svitkina, T. M. (2000) Actin machinery: pushing the envelope, Curr. Opin. Cell Biol., 12, 104–112.CrossRefGoogle Scholar
  53. 53.
    Svitkina, T. (2013) Ultrastructure of protrusive actin filament arrays, Curr. Opin. Cell Biol., 25, 574–581.PubMedCrossRefGoogle Scholar
  54. 54.
    Taunton, J. (2001) Actin filament nucleation by endosomes, lysosomes and secretory vesicles, Curr. Opin. Cell Biol., 13, 85–91.PubMedCrossRefGoogle Scholar
  55. 55.
    Kaksonen, M., Peng, H. B., and Rauvala, H. (2000) Association of cortactin with dynamic actin in lamellipodia and on endosomal vesicles, J. Cell Sci., 113, 4421–4426.PubMedGoogle Scholar
  56. 56.
    Zhang, F., Southwick, F. S., and Purich, D. L. (2002) Actin-based phagosome motility, Cell Motil. Cytoskeleton, 53, 81–88.PubMedCrossRefGoogle Scholar
  57. 57.
    Southwick, F. S., Li, W., Zhang, F., Zeile, W. L., and Purich, D. L. (2003) Actin-based endosome and phagosome rocketing in macrophages: activation by the secretagogue antagonists lanthanum and zinc, Cell Motil. Cytoskeleton, 54, 41–55.PubMedCrossRefGoogle Scholar
  58. 58.
    Pelkmans, L., Puntener, D., and Helenius, A. (2002) Local actin polymerization and dynamin recruitment in SV40-induced internalization of caveolae, Science, 296, 535–539.PubMedCrossRefGoogle Scholar
  59. 59.
    Schafer, D. A., D’Souza-Schorey, C., and Cooper, J. A. (2000) Actin assembly at membranes controlled by ARF6, Traffic, 1, 892–903.PubMedCrossRefGoogle Scholar
  60. 60.
    Boldogh, I. R., Yang, H.-C., Nowakowski, W. D., Karmon, S. L., Hays, L. G., Yates III, J. R., and Pon, L. A. (2001) Arp2/3 complex and actin dynamics are required for actin-based mitochondrial motility in yeast, Proc. Natl. Acad. Sci. USA, 98, 63162–63167.CrossRefGoogle Scholar
  61. 61.
    Bazinet, C., and Rollins, J. E. (2003) Rickettsia-like mitochondrial motility in Drosophila spermiogenesis, Evol. Dev., 5, 379–385.PubMedCrossRefGoogle Scholar
  62. 62.
    Merrifield, C. J. (2004) Seeing is believing: imaging actin dynamics at single sites of endocytosis, Trends Cell Biol., 14, 352–358.PubMedCrossRefGoogle Scholar
  63. 63.
    Merrifield, C. J., Perrais, D., and Zenisek, D. (2005) Coupling between clathrin-coated-pit invagination, cortactin recruitment, and membrane scission observed in live cells, Cell, 121, 593–606.PubMedCrossRefGoogle Scholar
  64. 64.
    Collins, A., Warrington, A., Taylor, K. A., and Svitkina, T. (2011) Structural organization of the actin cytoskeleton at sites of clathrin-mediated endocytosis, Curr. Biol., 21, 1167–1175.PubMedCrossRefPubMedCentralGoogle Scholar
  65. 65.
    Schmid, S. L., and Frolov, V. A. (2011) Dynamin: functional design of a membrane fission catalyst, Annu. Rev. Cell. Dev. Biol., 27, 79–105.PubMedCrossRefGoogle Scholar
  66. 66.
    Ferguson, S. M., and De Camilli, P. (2012) Dynamin, a membrane-remodeling GTPase, Nat. Rev. Mol. Cell Biol., 13, 75–88.PubMedPubMedCentralGoogle Scholar
  67. 67.
    Menon, M., and Schafer, D. A. (2013) Dynamin: expanding its scope to the cytoskeleton, Int. Rev. Cell. Mol. Biol., 302, 187–219.PubMedCrossRefGoogle Scholar
  68. 68.
    Conner, S. D., and Schmid, S. L. (2003) Regulated portals of entry into the cell, Nature, 422, 37–44.PubMedCrossRefGoogle Scholar
  69. 69.
    Yarar, D., Waterman-Storer, C. M., and Schmid, S. L. A. (2005) Dynamic actin cytoskeleton functions at multiple stages of clathrin-mediated endocytosis, Mol. Biol. Cell, 16, 964–975.PubMedCrossRefPubMedCentralGoogle Scholar
  70. 70.
    Lee, E., and De Camilli, P. (2002) Dynamin at actin tails, Proc. Natl. Acad. Sci. USA, 99, 161–166.PubMedCrossRefPubMedCentralGoogle Scholar
  71. 71.
    Daly, R. J. (2004) Cortactin signaling and dynamic actin networks, Biochem. J., 382, 13–25.PubMedCrossRefPubMedCentralGoogle Scholar
  72. 72.
    Hartig, S. M., Ishikura, S., Hicklen, R. S., Feng, Y., Blanchard, E. G., Voelker, K. A., Pichot, C. S., Grange, R. W., Raphael, R. M., Klip, A., and Corey, S. J. (2009) The F-BAR protein CIP4 promotes GLUT4 endocytosis through bidirectional interactions with N-WASp and Dynamin-2, J. Cell Sci., 122, 2283–2291.PubMedCrossRefPubMedCentralGoogle Scholar
  73. 73.
    Gu, C., Yaddanapudi, S., Weins, A., Osborn, T., Reiser, J., Pollak, M., Hartwig, J., and Sever, S. (2010) Direct dynamin-actin interactions regulate the actin cytoskeleton, EMBO J., 29, 3593–3606.PubMedCrossRefPubMedCentralGoogle Scholar
  74. 74.
    Taylor, M. J., Lampe, M., and Merrifield, C. J. (2012) A feedback loop between dynamin and actin recruitment during clathrin-mediated endocytosis, PLoS Biol., 10, e1001302.PubMedCrossRefPubMedCentralGoogle Scholar
  75. 75.
    Miller, L., Phillips, M., and Reisler, E. (1988) Polymerization of G-actin by myosin subfragment 1, J. Biol. Chem., 263, 1996–2002.PubMedGoogle Scholar
  76. 76.
    Wawro, B., Khaitlina, S. Yu., Galinska-Rakoczy, A., and Strzelecka-Golaszewska, H. (2005) Role of DNase-I-binding loop in myosin subfragment 1-induced actin polymerization. Implications to the polymerization mechanism, Biophys. J., 88, 2883–2896.PubMedCrossRefPubMedCentralGoogle Scholar
  77. 77.
    Cheng, J., Grassart, A., and Drubin, D. G. (2012) Myosin 1E coordinated actin assembly and cargo trafficking during clathrin-mediated endocytosis, Mol. Biol. Cell, 23, 2891–2904.PubMedCrossRefPubMedCentralGoogle Scholar
  78. 78.
    Egea, G., Lazaro-Dieguez, F., and Vilella, M. (2006) Actin dynamics at the Golgi complex in mammalian cells, Curr. Opin. Cell Biol., 18, 168–178.PubMedCrossRefGoogle Scholar
  79. 79.
    Mooren, O. L., Galletta, B. J., and Cooper, J. A. (2012) Roles for actin assembly in endocytosis, Annu. Rev. Biochem., 81, 661–686.PubMedCrossRefGoogle Scholar

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© Pleiades Publishing, Ltd. 2014

Authors and Affiliations

  1. 1.Institute of CytologyRussian Academy of SciencesSt. PetersburgRussia

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