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:

Basal-to-apical cadherin flow at cell junctions

Abstract

Stable cell–cell adhesion is essential for maintaining tissue integrity, but cells are also able to relocate, implying the existence of mechanisms for coordinating cell adhesion and movement. Here, we show that, in some transformed lines, cadherin adhesion molecules exhibit a flow-like movement in a basal–apical direction at the cell junction and that this flow is associated with reorganizing actin filaments. Such flow also occurs in normal epithelial sheets, but solely at the junctions formed by moving cells. We propose that cadherin flow may provide a mechanism for facilitating the sliding of the two contacting cell membranes in morphogenetically active cell sheets.

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

Access options

Buy this article

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

Figure 1: Directional movement of VE-cadherin at cell junctions.
Figure 2: Analysis of cadherin and catenin domains required for cadherin flow.
Figure 3: Actin-dependent movement of VE-cadherin.
Figure 4: Cadherin dynamics in MDCK cells.

Similar content being viewed by others

References

  1. Gumbiner, B. M. Regulation of cadherin-mediated adhesion in morphogenesis. Nature Rev. Mol. Cell Biol. 6, 622–634 (2005).

    Article  CAS  Google Scholar 

  2. Wheelock, M. J. & Johnson, K. R. Cadherins as modulators of cellular phenotype. Annu. Rev. Cell Dev. Biol. 19, 207–235 (2003).

    Article  CAS  Google Scholar 

  3. Rimm, D. L., Koslov, E. R., Kebriaei, P., Cianci, C. D. & Morrow, J. S. α1(E)-catenin is an actin-binding and -bundling protein mediating the attachment of F-actin to the membrane adhesion complex. Proc. Natl Acad. Sci. USA 92, 8813–8817 (1995).

    Article  CAS  Google Scholar 

  4. Drees, F., Pokutta, S., Yamada, S., Nelson, W. J. & Weis, W. I. α-catenin is a molecular switch that binds E-cadherin-β-catenin and regulates actin-filament assembly. Cell 123, 903–915 (2005).

    Article  CAS  Google Scholar 

  5. Watabe, M., Nagafuchi, A., Tsukita, S. & Takeichi, M. Induction of polarized cell-cell association and retardation of growth by activation of the E-cadherin-catenin adhesion system in a dispersed carcinoma line. J. Cell Biol. 127, 247–256 (1994).

    Article  CAS  Google Scholar 

  6. Lin, C. H. & Forscher, P. Growth cone advance is inversely proportional to retrograde F-actin flow. Neuron 14, 763–771 (1995).

    Article  CAS  Google Scholar 

  7. Small, J. V. & Resch, G. P. The comings and goings of actin: coupling protrusion and retraction in cell motility. Curr. Opin. Cell Biol. 17, 517–523 (2005).

    Article  CAS  Google Scholar 

  8. Nicholson-Dykstra, S., Higgs, H. N. & Harris, E. S. Actin dynamics: growth from dendritic branches. Curr. Biol. 15, R346–R357 (2005).

    Article  CAS  Google Scholar 

  9. Ponti, A., Machacek, M., Gupton, S. L., Waterman-Storer, C. M. & Danuser, G. Two distinct actin networks drive the protrusion of migrating cells. Science 305, 1782–1786 (2004).

    Article  CAS  Google Scholar 

  10. Watanabe, N. & Mitchison, T. J. Single-molecule speckle analysis of actin filament turnover in lamellipodia. Science 295, 1083–1086 (2002).

    Article  CAS  Google Scholar 

  11. Rodriguez, O. C. et al. Conserved microtubule-actin interactions in cell movement and morphogenesis. Nature Cell Biol. 5, 599–609 (2003).

    Article  CAS  Google Scholar 

  12. Waterman-Storer, C. M., Salmon, W. C. & Salmon, E. D. Feedback interactions between cell-cell adherens junctions and cytoskeletal dynamics in newt lung epithelial cells. Mol. Biol. Cell 11, 2471–2483 (2000).

    Article  CAS  Google Scholar 

  13. Lewis, J. E. et al. Cross-talk between adherens junctions and desmosomes depends on plakoglobin. J. Cell Biol. 136, 919–934 (1997).

    Article  CAS  Google Scholar 

  14. Kobielak, A. & Fuchs, E. α-catenin: at the junction of intercellular adhesion and actin dynamics. Nature Rev. Mol. Cell Biol. 5, 614–625 (2004).

    Article  CAS  Google Scholar 

  15. Zhang, X. F., Schaefer, A. W., Burnette, D. T., Schoonderwoert, V. T. & Forscher, P. Rho-dependent contractile responses in the neuronal growth cone are independent of classical peripheral retrograde actin flow. Neuron 40, 931–944 (2003).

    Article  CAS  Google Scholar 

  16. Saitoh, M., Ishikawa, T., Matsushima, S., Naka, M. & Hidaka, H. Selective inhibition of catalytic activity of smooth muscle myosin light chain kinase. J. Biol. Chem. 262, 7796–7801 (1987).

    CAS  PubMed  Google Scholar 

  17. Uehata, M. et al. Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature 389, 990–994 (1997).

    Article  CAS  Google Scholar 

  18. Totsukawa, G. et al. Distinct roles of MLCK and ROCK in the regulation of membrane protrusions and focal adhesion dynamics during cell migration of fibroblasts. J. Cell Biol. 164, 427–439 (2004).

    Article  CAS  Google Scholar 

  19. Nishimura, K. et al. L1-dependent neuritogenesis involves ankyrinB that mediates L1-CAM coupling with retrograde actin flow. J. Cell Biol. 163, 1077–1088 (2003).

    Article  CAS  Google Scholar 

  20. Yamada, S., Pokutta, S., Drees, F., Weis, W. I. & Nelson, W. J. Deconstructing the cadherin-catenin-actin complex. Cell 123, 889–901 (2005).

    Article  CAS  Google Scholar 

  21. Niewiadomska, P., Godt, D. & Tepass, U. DE-Cadherin is required for intercellular motility during Drosophila oogenesis. J. Cell Biol. 144, 533–547 (1999).

    Article  CAS  Google Scholar 

  22. Park, C., Falls, W., Finger, J. H., Longo-Guess, C. M. & Ackerman, S. L. Deletion in Catna2, encoding αN-catenin, causes cerebellar and hippocampal lamination defects and impaired startle modulation. Nature Genet. 31, 279–284 (2002).

    Article  CAS  Google Scholar 

  23. Moriyoshi, K., Richards, L. J., Akazawa, C., O'Leary, D. D. & Nakanishi, S. Labeling neural cells using adenoviral gene transfer of membrane-targeted GFP. Neuron 16, 255–260 (1996).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank N. Matsuyoshi (Kyoto University) for VE-cadherin cDNA, and N. Watanabe (Kyoto University) for critical comments. This work was supported by a grant from the program Grants-in-Aid for Specially Promoted Research of the Ministry of Education, Science, Sports, and Culture of Japan.

Author information

Authors and Affiliations

Authors

Contributions

Y.K. conceived and performed the experiments. Y.K. and M.T. interpreted data and wrote the manuscript.

Corresponding author

Correspondence to Masatoshi Takeichi.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information

Supplementary figure S1, S2 and S3 (PDF 388 kb)

Supplementary Information

Supplementary Movie 1 (MOV 1126 kb)

Supplementary Information

Supplementary Movie 2 (MOV 2035 kb)

Supplementary Information

Supplementary Movie 3 (MOV 1711 kb)

Supplementary Information

Supplementary Movie 4 (MOV 1139 kb)

Supplementary Information

Supplementary Movie 5 (MOV 627 kb)

Supplementary Information

Supplementary Movie 6 (MOV 527 kb)

Supplementary Information

Supplementary Movie 7 (MOV 2931 kb)

Supplementary Information

Supplementary Movie 8 (MOV 602 kb)

Supplementary Information

Supplementary Movie 9 (MOV 944 kb)

Supplementary Information

Supplementary Movie 10 (MOV 2694 kb)

Supplementary Information

Supplementary Movie 11 (MOV 1137 kb)

Supplementary Information

Supplementary Movie 12 (MOV 1123 kb)

Supplementary Information

Supplementary Movie 13 (MOV 687 kb)

Supplementary Information

Supplementary Movie 14 (MOV 2564 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kametani, Y., Takeichi, M. Basal-to-apical cadherin flow at cell junctions. Nat Cell Biol 9, 92–98 (2007). https://doi.org/10.1038/ncb1520

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncb1520

This article is cited by

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