Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

An actin-dependent mechanism for long-range vesicle transport

Nature Cell Biology volume 13, pages 1431–1436 (2011)Cite this article

Subjects

Abstract

Intracellular transport is vital for the function, survival and architecture of every eukaryotic cell. Long-range transport in animal cells is thought to depend exclusively on microtubule tracks. This study reveals an unexpected actin-dependent but microtubule-independent mechanism for long-range transport of vesicles. Vesicles organize their own actin tracks by recruiting the actin nucleation factors Spire1, Spire2 and Formin-2, which assemble an extensive actin network from the vesicles’ surfaces. The network connects the vesicles with one another and with the plasma membrane. Vesicles move directionally along these connections in a myosin-Vb-dependent manner to converge and to reach the cell surface. The overall outward-directed movement of the vesicle-actin network is driven by recruitment of vesicles to the plasma membrane in the periphery of the oocyte. Being organized in a dynamic vesicle-actin network allows vesicles to move in a local random manner and a global directed manner at the same time: they can reach any position in the cytoplasm, but also move directionally to the cell surface as a collective. Thus, collective movement within a network is a powerful and flexible mode of vesicle transport.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Vesicles move over long distances to the cell surface.
Figure 2: Vesicle movements depend on actin instead of microtubules.
Figure 3: Spire1/2 and Fmn2 assemble actin tracks.
Figure 4: Vesicles organize an actin network.
Figure 5: Mechanism of directional vesicle transport.

Similar content being viewed by others

References

  1. Ross, J. L., Ali, M. Y. & Warshaw, D. M. Cargo transport: Molecular motors navigate a complex cytoskeleton. Curr. Opin. Cell Biol. 20, 41–47 (2008).

    Article  CAS  Google Scholar 

  2. Alberts, B. et al. Molecular Biology of the Cell 5th edn (Garland Science, 2008).

    Google Scholar 

  3. Lodish, H. et al. Molecular Cell Biology (W. H. Freeman, 2007).

    Google Scholar 

  4. Pollard, T. & Earnshaw, W. Cell Biology (Saunders, 2004).

    Google Scholar 

  5. Hirokawa, N., Noda, Y., Tanaka, Y. & Niwa, S. Kinesin superfamily motor proteins and intracellular transport. Nat. Rev. Mol. Cell Biol. 10, 682–696 (2009).

    Article  CAS  Google Scholar 

  6. Kardon, J. R. & Vale, R. D. Regulators of the cytoplasmic dynein motor. Nat. Rev. Mol. Cell Biol. 10, 854–865 (2009).

    Article  CAS  Google Scholar 

  7. Bloom, G. S. & Goldstein, L. S. Cruising along microtubule highways: how membranes move through the secretory pathway. J. Cell Biol. 140, 1277–1280 (1998).

    Article  CAS  Google Scholar 

  8. Apodaca, G. Endocytic traffic in polarized epithelial cells: role of the actin and microtubule cytoskeleton. Traffic 2, 149–159 (2001).

    Article  CAS  Google Scholar 

  9. Fackler, O. T. & Krausslich, H. G. Interactions of human retroviruses with the host cell cytoskeleton. Curr. Opin. Microbiol. 9, 409–415 (2006).

    Article  CAS  Google Scholar 

  10. Woolner, S. & Bement, W. M. Unconventional myosins acting unconventionally. Trends Cell Biol. 19, 245–252 (2009).

    Article  CAS  Google Scholar 

  11. Wang, Z. et al. Myosin Vb mobilizes recycling endosomes and AMPA receptors for postsynaptic plasticity. Cell 135, 535–548 (2008).

    Article  CAS  Google Scholar 

  12. Wagner, W., Brenowitz, S. D. & Hammer, J. A. 3rd Myosin-Va transports the endoplasmic reticulum into the dendritic spines of Purkinje neurons. Nat. Cell Biol. 13, 40–48 (2011).

    Article  CAS  Google Scholar 

  13. Wu, X., Bowers, B., Rao, K., Wei, Q. & Hammer, J. A. 3rd Visualization of melanosome dynamics within wild-type and dilute melanocytes suggests a paradigm for myosin V function in vivo. J. Cell Biol. 143, 1899–1918 (1998).

    Article  CAS  Google Scholar 

  14. Stenmark, H. Rab GTPases as coordinators of vesicle traffic. Nat. Rev. Mol. Cell Biol. 10, 513–525 (2009).

    Article  CAS  Google Scholar 

  15. Grant, B. D. & Donaldson, J. G. Pathways and mechanisms of endocytic recycling. Nat. Rev. Mol. Cell Biol. 10, 597–608 (2009).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  17. Soldati, T. & Schliwa, M. Powering membrane traffic in endocytosis and recycling. Nat. Rev. Mol. Cell Biol. 7, 897–908 (2006).

    Article  CAS  Google Scholar 

  18. Schuh, M. & Ellenberg, J. Self-organization of MTOCs replaces centrosome function during acentrosomal spindle assembly in live mouse oocytes. Cell 130, 484–498 (2007).

    Article  CAS  Google Scholar 

  19. Pfender, S., Kuznetsov, V., Pleiser, S., Kerkhoff, E. & Schuh, M. Spire-type actin nucleators cooperate with Formin-2 to drive asymmetric oocyte division. Curr. Biol. 21, 955–960 (2011).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  21. Nolen, B. J. et al. Characterization of two classes of small molecule inhibitors of Arp2/3 complex. Nature 460, 1031–1034 (2009).

    Article  CAS  Google Scholar 

  22. Ito, T. et al. Human spire interacts with the barbed end of the actin filament. J. Mol. Biol. 408, 18–25 (2011).

    Article  CAS  Google Scholar 

  23. 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).

    Article  CAS  Google Scholar 

  24. Campellone, K. G. & Welch, M. D. A nucleator arms race: cellular control of actin assembly. Nat. Rev. Mol. Cell Biol. 11, 237–251 (2010).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  26. Lapierre, L. A. et al. Myosin vb is associated with plasma membrane recycling systems. Mol. Biol. Cell 12, 1843–1857 (2001).

    Article  CAS  Google Scholar 

  27. Watanabe, S., Mabuchi, K., Ikebe, R. & Ikebe, M. Mechanoenzymatic characterization of human myosin Vb. Biochemistry 45, 2729–2738 (2006).

    Article  CAS  Google Scholar 

  28. Begg, D. A. & Rebhun, L. I. pH regulates the polymerization of actin in the sea urchin egg cortex. J. Cell Biol. 83, 241–248 (1979).

    Article  CAS  Google Scholar 

  29. Kerkhoff, E. et al. The Spir actin organizers are involved in vesicle transport processes. Curr. Biol. 11, 1963–1968 (2001).

    Article  CAS  Google Scholar 

  30. Gomez, T. S. & Billadeau, D. D. A FAM21-containing WASH complex regulates retromer-dependent sorting. Dev. Cell 17, 699–711 (2009).

    Article  CAS  Google Scholar 

  31. Morel, E., Parton, R. G. & Gruenberg, J. Annexin A2-dependent polymerization of actin mediates endosome biogenesis. Dev. Cell 16, 445–457 (2009).

    Article  CAS  Google Scholar 

  32. Galletta, B. J. & Cooper, J. A. Actin and endocytosis: mechanisms and phylogeny. Curr. Opin. Cell Biol. 21, 20–27 (2009).

    Article  CAS  Google Scholar 

  33. Woolner, S., O’Brien, L. L., Wiese, C. & Bement, W. M. Myosin-10 and actin filaments are essential for mitotic spindle function. J. Cell Biol. 182, 77–88 (2008).

    Article  CAS  Google Scholar 

  34. Rauzi, M., Lenne, P. F. & Lecuit, T. Planar polarized actomyosin contractile flows control epithelial junction remodelling. Nature 468, 1110–1114 (2010).

    Article  CAS  Google Scholar 

  35. 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).

    Article  CAS  Google Scholar 

  36. Munro, E., Nance, J. & Priess, J. R. Cortical flows powered by asymmetrical contraction transport PAR proteins to establish and maintain anterior-posterior polarity in the early C. elegans embryo. Dev. Cell 7, 413–424 (2004).

    Article  CAS  Google Scholar 

  37. Jaffe, L. A., Norris, R. P., Freudzon, M., Ratzan, W. J. & Mehlmann, L. M. Microinjection of follicle-enclosed mouse oocytes. Methods Mol. Biol. 518, 157–173 (2009).

    Article  CAS  Google Scholar 

  38. Eppig, J. J. & Schroeder, A. C. Capacity of mouse oocytes from preantral follicles to undergo embryogenesis and development to live young after growth, maturation, and fertilization in vitro. Biol. Reprod. 41, 268–276 (1989).

    Article  CAS  Google Scholar 

  39. Strickland, L. et al. Light microscopy of echinoderm embryos. Methods Cell Biol. 74, 371–409 (2004).

    Article  Google Scholar 

  40. Shaner, N. C. et al. Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein. Nat. Biotechnol. 22, 1567–1572 (2004).

    Article  CAS  Google Scholar 

  41. Sonnichsen, B., De Renzis, S., Nielsen, E., Rietdorf, J. & Zerial, M. Distinct membrane domains on endosomes in the recycling pathway visualized by multicolor imaging of Rab4, Rab5, and Rab11. J. Cell Biol. 149, 901–914 (2000).

    Article  CAS  Google Scholar 

  42. Aschenbrenner, L., Lee, T. & Hasson, T. Myo6 facilitates the translocation of endocytic vesicles from cell peripheries. Mol. Biol. Cell 14, 2728–2743 (2003).

    Article  CAS  Google Scholar 

  43. Bittins, C. M., Eichler, T. W., Hammer, J. A. 3rd & Gerdes, H. H. Dominant-negative myosin Va impairs retrograde but not anterograde axonal transport of large dense core vesicles. Cell Mol. Neurobiol. 30, 369–379 (2010).

    Article  Google Scholar 

  44. Liman, E. R., Tytgat, J. & Hess, P. Subunit stoichiometry of a mammalian K+ channel determined by construction of multimeric cDNAs. Neuron 9, 861–871 (1992).

    Article  CAS  Google Scholar 

  45. Burkel, B. M., von Dassow, G. & Bement, W. M. Versatile fluorescent probes for actin filaments based on the actin-binding domain of utrophin. Cell Motil. Cytoskeleton 64, 822–832 (2007).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The author thanks P. Leder, B. Leader and M. Dettenhofer for Fmn2−/− mice; the staff of the LMB’s Animal Facility for expert technical assistance; and M. Freeman, S. Munro and B. Nichols for helpful discussions and critical reading of the manuscript. The research leading to these results has received financial support from the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 241548.

Author information

Authors and Affiliations

  1. Medical Research Council, Laboratory of Molecular Biology, Cambridge CB2 0QH, UK

    Melina Schuh

Authors
  1. Melina Schuh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Melina Schuh.

Ethics declarations

Competing interests

The author declares no competing financial interests.

Supplementary information

Supplementary Information

Supplementary Information (PDF 1046 kb)

Supplementary movie 1

Supplementary Information (MOV 3272 kb)

Supplementary movie 2

Supplementary Information (MOV 11025 kb)

Supplementary movie 3

Supplementary Information (MOV 8589 kb)

Supplementary movie 4

Supplementary Information (MOV 8356 kb)

Supplementary movie 5

Supplementary Information (MOV 8899 kb)

Supplementary movie 6

Supplementary Information (MOV 3447 kb)

Supplementary movie 7

Supplementary Information (MOV 778 kb)

Supplementary movie 8

Supplementary Information (MOV 8791 kb)

Supplementary movie 9

Supplementary Information (MOV 1880 kb)

Supplementary movie 10

Supplementary Information (MOV 1860 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schuh, M. An actin-dependent mechanism for long-range vesicle transport. Nat Cell Biol 13, 1431–1436 (2011). https://doi.org/10.1038/ncb2353

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncb2353

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing