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.

  • Opinion
  • Published:

Understanding eukaryotic chemotaxis: a pseudopod-centred view

Nature Reviews Molecular Cell Biology volume 11, pages 453–458 (2010)Cite this article

Subjects

Abstract

Current descriptions of eukaryotic chemotaxis and cell movement focus on how extracellular signals (chemoattractants) cause new pseudopods to form. This 'signal-centred' approach is widely accepted but is derived mostly from special cases, particularly steep chemoattractant gradients. I propose a 'pseudopod-centred' explanation, whereby most pseudopods form themselves, without needing exogenous signals, and chemoattractants only bias internal pseudopod dynamics. This reinterpretation of recent data suggests that future research should focus on pseudopod mechanics, not signal processing.

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: Pseudopod generation during cell turning.
Figure 2: Models of chemotaxis.

Similar content being viewed by others

References

  1. Bray, D. Cell movements: from molecules to motility (Garland Science, 2000).

    Google Scholar 

  2. Swaney, K. F., Huang, C. H. & Devreotes, P. N. Eukaryotic chemotaxis: a network of signaling pathways controls motility, directional sensing, and polarity. Annu. Rev. Biophys. 2 Feb 2010 (doi: 10.1146/annurev.biophys.093008.131228).

  3. Weiner, O. D. et al. A PtdInsP(3)- and Rho GTPase-mediated positive feedback loop regulates neutrophil polarity. Nature Cell Biol. 4, 509–513 (2002).

    Article  CAS  PubMed  Google Scholar 

  4. Gerisch, G. & Keller, H. U. Chemotactic reorientation of granulocytes stimulated with micropipettes containing fMet-Leu-Phe. J. Cell Sci. 52, 1–10 (1981).

    CAS  PubMed  Google Scholar 

  5. Parent, C. A., Blacklock, B. J., Froehlich, W. M., Murphy, D. B. & Devreotes, P. N. G protein signaling events are activated at the leading edge of chemotactic cells. Cell 95, 81–91 (1998).

    Article  CAS  PubMed  Google Scholar 

  6. Rickert, P., Weiner, O. D., Wang, F., Bourne, H. R. & Servant, G. Leukocytes navigate by compass: roles of PI3Kγ and its lipid products. Trends Cell Biol. 10, 466–473 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. van Rheenen, J. et al. EGF-induced PIP2 hydrolysis releases and activates cofilin locally in carcinoma cells. J. Cell Biol. 179, 1247–1259 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Maeda, Y. T., Inose, J., Matsuo, M. Y., Iwaya, S. & Sano, M. Ordered patterns of cell shape and orientational correlation during spontaneous cell migration. PLoS ONE 3, e3734 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Li, L., Norrelykke, S. F. & Cox, E. C. Persistent cell motion in the absence of external signals: a search strategy for eukaryotic cells. PLoS ONE 3, e2093 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  10. Bosgraaf, L. & Van Haastert, P. J. The ordered extension of pseudopodia by amoeboid cells in the absence of external cues. PLoS One 4, e5253 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Devreotes, P. & Janetopoulos, C. Eukaryotic chemotaxis: distinctions between directional sensing and polarization. J. Biol. Chem. 278, 20445–20448 (2003).

    Article  CAS  PubMed  Google Scholar 

  12. Postma, M. et al. Sensitization of Dictyostelium chemotaxis by phosphoinositide-3-kinase-mediated self-organizing signalling patches. J. Cell Sci. 117, 2925–2935 (2004).

    Article  CAS  PubMed  Google Scholar 

  13. Arrieumerlou, C. & Meyer, T. A local coupling model and compass parameter for eukaryotic chemotaxis. Dev. Cell 8, 215–227 (2005).

    Article  CAS  PubMed  Google Scholar 

  14. Ferguson, G. J. et al. PI(3)Kγ has an important context-dependent role in neutrophil chemokinesis. Nature Cell Biol. 9, 86–91 (2007).

    Article  CAS  PubMed  Google Scholar 

  15. Hoeller, O. & Kay, R. R. Chemotaxis in the absence of PIP3 gradients. Curr. Biol. 17, 813–817 (2007).

    Article  CAS  PubMed  Google Scholar 

  16. Heit, B., Liu, L., Colarusso, P., Puri, K. D. & Kubes, P. PI3K accelerates, but is not required for, neutrophil chemotaxis to fMLP. J. Cell Sci. 121, 205–214 (2008).

    Article  CAS  PubMed  Google Scholar 

  17. Chen, L. et al. PLA2 and PI3K/PTEN pathways act in parallel to mediate chemotaxis. Dev. Cell 12, 603–614 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Veltman, D. M. & van Haastert, P. J. The role of cGMP and the rear of the cell in Dictyostelium chemotaxis and cell streaming. J. Cell Sci. 121, 120–127 (2008).

    Article  CAS  PubMed  Google Scholar 

  19. Veltman, D. M., Keizer-Gunnik, I. & Van Haastert, P. J. Four key signaling pathways mediating chemotaxis in Dictyostelium discoideum. J. Cell Biol. 180, 747–753 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Andrew, N. & Insall, R. H. Chemotaxis in shallow gradients is mediated independently of PtdIns 3-kinase by biased choices between random protrusions. Nature Cell Biol. 9, 193–200 (2007).

    Article  CAS  PubMed  Google Scholar 

  21. Martini, F. J. et al. Biased selection of leading process branches mediates chemotaxis during tangential neuronal migration. Development 136, 41–50 (2009).

    Article  CAS  PubMed  Google Scholar 

  22. Cvejic, A. et al. Analysis of WASp function during the wound inflammatory response — live-imaging studies in zebrafish larvae. J. Cell Sci. 121, 3196–3206 (2008).

    Article  CAS  PubMed  Google Scholar 

  23. Bosgraaf, L. & Van Haastert, P. J. Navigation of chemotactic cells by parallel signaling to pseudopod persistence and orientation. PLoS One 4, e6842 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  24. Chubb, J. R., Wilkins, A., Wessels, D. J., Soll, D. R. & Insall, R. H. Pseudopodium dynamics and rapid cell movement in Dictyostelium Ras pathway mutants. Cell. Motil. Cytoskeleton 53, 150–162 (2002).

    Article  CAS  PubMed  Google Scholar 

  25. Murray, J., Vawter-Hugart, H., Voss, E. & Soll, D. R. Three-dimensional motility cycle in leukocytes. Cell. Motil. Cytoskeleton 22, 211–223 (1992).

    Article  CAS  PubMed  Google Scholar 

  26. Gerisch, G., Hulser, D., Malchow, D. & Wick, U. Cell communication by periodic cyclic-AMP pulses. Philos. Trans. R. Soc. Lond. B Biol. Sci. 272, 181–192 (1975).

    Article  CAS  PubMed  Google Scholar 

  27. Franca-Koh, J., Kamimura, Y. & Devreotes, P. N. Leading-edge research: PtdIns(3, 4, 5)P3 and directed migration. Nature Cell Biol. 9, 15–17 (2007).

    Article  CAS  PubMed  Google Scholar 

  28. Korohoda, W., Drukala, J., Sroka, J. & Madeja, Z. Isolation, spreading, locomotion on various substrata, and the effect of hypotonicity on locomotion of fish keratinocytes. Biochem. Cell Biol. 75, 277–286 (1997).

    Article  CAS  PubMed  Google Scholar 

  29. Wu, L., Valkema, R., Van Haastert, P. J. & Devreotes, P. N. The G protein β subunit is essential for multiple responses to chemoattractants in Dictyostelium. J. Cell Biol. 129, 1667–1675 (1995).

    Article  CAS  PubMed  Google Scholar 

  30. Peracino, B. et al. G protein β subunit-null mutants are impaired in phagocytosis and chemotaxis due to inappropriate regulation of the actin cytoskeleton. J. Cell Biol. 141, 1529–1537 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Insall, R. H. & Weiner, O. D. PIP3, PIP2, and cell movement — similar messages, different meanings? Dev. Cell 1, 743–747 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Iijima, M. & Devreotes, P. Tumor suppressor PTEN mediates sensing of chemoattractant gradients. Cell 109, 599–610 (2002).

    Article  CAS  PubMed  Google Scholar 

  33. McRobbie, S. J. & Newell, P. C. Chemoattractant-mediated changes in cytoskeletal actin of cellular slime moulds. J. Cell Sci. 68, 139–151 (1984).

    CAS  PubMed  Google Scholar 

  34. Letinic, K., Sebastian, R., Toomre, D. & Rakic, P. Exocyst is involved in polarized cell migration and cerebral cortical development. Proc. Natl Acad. Sci. USA 106, 11342–11347 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Van Haastert, P. J. & Devreotes, P. N. Chemotaxis: signalling the way forward. Nature Rev. Mol. Cell Biol. 5, 626–634 (2004).

    Article  CAS  Google Scholar 

  36. Killich, T. et al. The locomotion, shape and pseudopodial dynamics of unstimulated Dictyostelium cells are not random. J. Cell Sci. 106, 1005–1013 (1993).

    PubMed  Google Scholar 

  37. Weiner, O. D., Marganski, W. A., Wu, L. F., Altschuler, S. J. & Kirschner, M. W. An actin-based wave generator organizes cell motility. PLoS Biol. 5, e221 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  38. Meinhardt, H. Orientation of chemotactic cells and growth cones: models and mechanisms. J. Cell Sci. 112, 2867–2874 (1999).

    CAS  PubMed  Google Scholar 

  39. Brandman, O. & Meyer, T. Feedback loops shape cellular signals in space and time. Science 322, 390–395 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Mouneimne, G. et al. Phospholipase C and cofilin are required for carcinoma cell directionality in response to EGF stimulation. J. Cell Biol. 166, 697–708 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Schneider, I. C. & Haugh, J. M. Quantitative elucidation of a distinct spatial gradient-sensing mechanism in fibroblasts. J. Cell Biol. 171, 883–892 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Bosgraaf, L., Keizer-Gunnink, I. & Van Haastert, P. J. PI3-kinase signaling contributes to orientation in shallow gradients and enhances speed in steep chemoattractant gradients. J. Cell Sci. 121, 3589–3597 (2008).

    Article  CAS  PubMed  Google Scholar 

  43. Carter, S. B. Haptotaxis and the mechanism of cell motility. Nature 213, 256–260 (1967).

    Article  CAS  PubMed  Google Scholar 

  44. Decave, E. et al. Shear flow-induced motility of Dictyostelium discoideum cells on solid substrate. J. Cell Sci. 116, 4331–4343 (2003).

    Article  CAS  PubMed  Google Scholar 

  45. Zhao, M. et al. Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-γ and PTEN. Nature 442, 457–460 (2006).

    Article  CAS  PubMed  Google Scholar 

  46. Killich, T. et al. Cell movement and shape are non-random and determined by intracellular, oscillatory rotating waves in Dictyostelium amoebae. Biosystems 33, 75–87 (1994).

    Article  CAS  PubMed  Google Scholar 

  47. Vicker, M. G. & Grutsch, J. F. Dual chemotaxis signalling regulates Dictyostelium development: intercellular cyclic AMP pulses and intracellular F-actin disassembly waves induce each other. Eur. J. Cell Biol., 87, 845–861 (2008).

    Article  CAS  Google Scholar 

  48. Millius, A., Dandekar, S. N., Houk, A. R. & Weiner, O. D. Neutrophils establish rapid and robust WAVE complex polarity in an actin-dependent fashion. Curr. Biol. 19, 253–259 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Ibarra, N., Blagg, S. L., Vazquez, F. & Insall, R. H. Nap1 regulates Dictyostelium cell motility and adhesion through SCAR-dependent and -independent pathways. Curr. Biol. 16, 717–722 (2006).

    Article  CAS  PubMed  Google Scholar 

  50. Bray, D., Levin, M. D. & Lipkow, K. The chemotactic behavior of computer-based surrogate bacteria. Curr. Biol. 17, 12–19 (2007).

    Article  CAS  PubMed  Google Scholar 

  51. Devreotes, P. N. & Zigmond, S. H. Chemotaxis in eukaryotic cells: a focus on leukocytes and Dictyostelium. Annu. Rev. Cell Biol. 4, 649–686 (1988).

    Article  CAS  PubMed  Google Scholar 

  52. Haugwitz, M., Noegel, A. A., Karakesisoglou, J. & Schleicher, M. Dictyostelium amoebae that lack G-actin-sequestering profilins show defects in F-actin content, cytokinesis, and development. Cell 79, 303–314 (1994).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

I am grateful to P. Thomason, D. Veltman, K. Anderson, G. Weeks, G. Jones and L. Machesky for critical comments on this manuscript.

Author information

Authors and Affiliations

  1. Robert H. Insall is at the Beatson Institute for Cancer Research, Bearsden, Glasgow G61 1BD, UK r.insall@beatson.gla.ac.uk,

    Robert H. Insall

Authors
  1. Robert H. Insall
    View author publications

    You can also search for this author in PubMed Google Scholar

Ethics declarations

Competing interests

The author declares no competing financial interests.

Related links

Related links

FURTHER INFORMATION

Robert H. Insall's homepage

Rights and permissions

Reprints and permissions

About this article

Cite this article

Insall, R. Understanding eukaryotic chemotaxis: a pseudopod-centred view. Nat Rev Mol Cell Biol 11, 453–458 (2010). https://doi.org/10.1038/nrm2905

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrm2905

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