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.

Functional atlas of the integrin adhesome

Nature Cell Biology volume 9, pages 858–867 (2007)Cite this article

Abstract

A detailed depiction of the 'integrin adhesome', consisting of a complex network of 156 components linked together and modified by 690 interactions is presented. Different views of the network reveal several functional 'subnets' that are involved in switching on or off many of the molecular interactions within the network, consequently affecting cell adhesion, migration and cytoskeletal organization. Examination of the adhesome network motifs reveals a relatively small number of key motifs, dominated by three-component complexes in which a scaffolding molecule recruits both a signalling molecule and its downstream target. We discuss the role of the different network modules in regulating the structural and signalling functions of cell–matrix adhesions.

Your institute does not have access to this article

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

Figure 1: Interactions between all intrinsic components of the adhesome and a grouped list of the associated components.
Figure 2: Interactions between functional families of adhesome components.
Figure 3: Actin–integrin subnet interconnecting the membrane receptors (mainly integrin) with actin.
Figure 4: Phosphorylation subnets mapping serine/threonine kinases and phosphatases (a) and tyrosine kinases and phosphatases (b).
Figure 5: GTPase, lipid and proteolytic subnets.
Figure 6: Phosphorylation switches regulating specific phosphotyrosine–SH2 domain interactions.
Figure 7: Network motifs of the adhesome.

References

  1. Burridge, K., Fath, K., Kelly, T., Nuckolls, G. & Turner, C. Focal adhesions: transmembrane junctions between the extracellular matrix and the cytoskeleton. Annu. Rev. Cell Biol. 4, 487–525 (1988).

    CAS  Article  Google Scholar 

  2. Geiger, B., Bershadsky, A., Pankov, R. & Yamada, K. M. Transmembrane crosstalk between the extracellular matrix — cytoskeleton crosstalk. Nature Rev. Mol. Cell. Biol. 2, 793–805 (2001).

    CAS  Article  Google Scholar 

  3. Critchley, D. R. et al. Integrin-mediated cell adhesion: the cytoskeletal connection. Biochem. Soc. Symp. 65, 79–99 (1999).

    CAS  PubMed  Google Scholar 

  4. Geiger, B. & Bershadsky, A. Exploring the neighborhood: adhesion-coupled cell mechanosensors. Cell 110, 139–142 (2002).

    CAS  Article  Google Scholar 

  5. Bershadsky, A., Kozlov, M. & Geiger, B. Adhesion-mediated mechanosensitivity: a time to experiment, and a time to theorize. Curr. Opin. Cell Biol. 18, 472–481 (2006).

    CAS  Article  Google Scholar 

  6. Cukierman, E., Pankov, R., Stevens, D. R. & Yamada, K. M. Taking cell-matrix adhesions to the third dimension. Science 294, 1708–1712 (2001).

    CAS  Article  Google Scholar 

  7. Humphries, M. J. The molecular basis and specificity of integrin-ligand interactions. J. Cell Sci. 97, 585–592 (1990).

    CAS  PubMed  Google Scholar 

  8. Cavalcanti-Adam, E. A. et al. Lateral spacing of integrin ligands influences cell spreading and focal adhesion assembly. Eur. J. Cell Biol. 85, 219–224 (2006).

    CAS  Article  Google Scholar 

  9. Lo, C. M., Wang, H. B., Dembo, M. & Wang, Y. L. Cell movement is guided by the rigidity of the substrate. Biophys. J. 79, 144–152 (2000).

    CAS  Article  Google Scholar 

  10. Zaidel-Bar, R., Kam, Z. & Geiger, B. Polarized downregulation of the paxillin–p130CAS–Rac1 pathway induced by shear flow. J. Cell Sci. 118, 3997–4007 (2005).

    CAS  Article  Google Scholar 

  11. Brown, M. C. & Turner, C. E. Paxillin: adapting to change. Physiol. Rev. 84, 1315–1339 (2004).

    CAS  Article  Google Scholar 

  12. Legate, K. R., Montanez, E., Kudlacek, O. & Fassler, R. ILK, PINCH and parvin: the tIPP of integrin signalling. Nature Rev. Mol. Cell Biol. 7, 20–31 (2006).

    CAS  Article  Google Scholar 

  13. Lo, S. H. Focal adhesions: what's new inside. Dev. Biol. 294, 280–291 (2006).

    CAS  Article  Google Scholar 

  14. Zamir, E. & Geiger, B. Molecular complexity and dynamics of cell-matrix adhesions. J. Cell Sci. 114, 3583–3590 (2001).

    CAS  PubMed  Google Scholar 

  15. Zamir, E. & Geiger, B. Components of cell-matrix adhesions. J. Cell Sci. 114, 3577–3579 (2001).

    CAS  PubMed  Google Scholar 

  16. Bader, G. D., Betel, D. & Hogue, C. W. BIND: the Biomolecular Interaction Network Database. Nucleic Acids Res. 31, 248–250 (2003).

    CAS  Article  Google Scholar 

  17. Mishra, G. R. et al. Human protein reference database — 2006 update. Nucleic Acids Res. 34, D411–D414 (2006).

    CAS  Article  Google Scholar 

  18. Shannon, P. et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 13, 2498–2504 (2003).

    CAS  Article  Google Scholar 

  19. Collins, M. O. et al. Molecular characterization and comparison of the components and multiprotein complexes in the postsynaptic proteome. J. Neurochem. 97, 16–23 (2005).

    Article  Google Scholar 

  20. Iragne, F., Nikolski, M., Mathieu, B., Auber, D. & Sherman, D. ProViz: protein interaction visualization and exploration. Bioinformatics 21, 272–274 (2005).

    CAS  Article  Google Scholar 

  21. Zanzoni, A. et al. MINT: a Molecular INTeraction database. FEBS Lett. 513, 135–140 (2002).

    CAS  Article  Google Scholar 

  22. Xenarios, I. et al. DIP: the database of interacting proteins. Nucleic Acids Res. 28, 289–291 (2000).

    CAS  Article  Google Scholar 

  23. Rual, J. F. et al. Towards a proteome-scale map of the human protein-protein interaction network. Nature 437, 1173–1178 (2005).

    CAS  Article  Google Scholar 

  24. Stelzl, U. et al. A human protein-protein interaction network: a resource for annotating the proteome. Cell 122, 957–968 (2005).

    CAS  Article  Google Scholar 

  25. Watts, D. J. & Strogatz, S. H. Collective dynamics of 'small-world' networks. Nature 393, 440–442 (1998).

    CAS  Article  Google Scholar 

  26. Caldarelli, G., Pastor-Satorras, R. & Vespignani, A. Structure of cycles and local ordering in complex networks. Eur. Phys. J. B 38, 183–186 (2004).

    CAS  Article  Google Scholar 

  27. Jeong, H., Mason, S. P., Barabasi, A. L. & Oltvai, Z. N. Lethality and centrality in protein networks. Nature 411, 41–42 (2001).

    CAS  Article  Google Scholar 

  28. Albert, R., Jeong, H. & Barabasi, A. L. Error and attack tolerance of complex networks. Nature 406, 378–382 (2000).

    CAS  Article  Google Scholar 

  29. Soriano, P., Montgomery, C., Geske, R. & Bradley, A. Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice. Cell 64, 693–702 (1991).

    CAS  Article  Google Scholar 

  30. Parsons, S. J. & Parsons, J. T. Src family kinases, key regulators of signal transduction. Oncogene 23, 7906–7909 (2004).

    CAS  Article  Google Scholar 

  31. Gough, N. R. & Ray, L. B. Mapping cellular signaling. Sci STKE 135, EG8 (2002).

    Google Scholar 

  32. Ma'ayan, A., Blitzer, R. D. & Iyengar, R. Toward predictive models of mammalian cells. Annu. Rev. Biophys. Biomol. Struct. 34, 319–349 (2005).

    CAS  Article  Google Scholar 

  33. Mostafavi-Pour, Z. et al. Integrin-specific signaling pathways controlling focal adhesion formation and cell migration. J. Cell Biol. 161, 155–167 (2003).

    CAS  Article  Google Scholar 

  34. Mangan, S. & Alon, U. Structure and function of the feed-forward loop network motif. Proc. Natl Acad. Sci. USA 100, 11980–11985 (2003).

    CAS  Article  Google Scholar 

  35. Alon, U. Biological networks: the tinkerer as an engineer. Science 301, 1866–1867 (2003).

    CAS  Article  Google Scholar 

  36. Shen-Orr, S. S., Milo, R., Mangan, S. & Alon, U. Network motifs in the transcriptional regulation network of Escherichia coli. Nature Genet. 31, 64–68 (2002).

    CAS  Article  Google Scholar 

  37. Milo, R. et al. Network motifs: simple building blocks of complex networks. Science 298, 824–827 (2002).

    CAS  Article  Google Scholar 

  38. Kashtan, N., Itzkovitz, S., Milo, R. & Alon, U. Efficient sampling algorithm for estimating subgraph concentrations and detecting network motifs. Bioinformatics 20, 1746–1758 (2004).

    CAS  Article  Google Scholar 

Download references

Acknowledgements

This project is funded in part by a National Institutes of Health (NIH) NanoMedicine Center for Mechanical Biology (GM-54508), Advanced Research Center Grant NYSTAR from New York State to R.I. and National Institute of General Medical Science (NIGMS) grant for the Cell Migration Consortium (NIH Grant U54 GM64346), and the United States-Israel Bionational Science Foundation. B.G. holds the Erwin Neter Professorial Chair in Cell and Tumor Biology.

Author information

Authors and Affiliations

  1. Shalev Itzkovitz and Benjamin Geiger are at the Department of Molecular Cell Biology, Ronen Zaidel-Bar, Weizmann Institute of Science, Rehovot, 76100, Israel. benny.geiger@weizmann.ac.il,

    Ronen Zaidel-Bar, Shalev Itzkovitz & Benjamin Geiger

  2. Avi Ma'ayan and Ravi Iyengar are at the Department of Pharmacology & Biological Chemistry, Mount Sinai School of Medicine, New York, NY 10029, USA.,

    Avi Ma'ayan & Ravi Iyengar

Authors
  1. Ronen Zaidel-Bar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shalev Itzkovitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Avi Ma'ayan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ravi Iyengar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Benjamin Geiger
    View author publications

    You can also search for this author in PubMed Google Scholar

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Zaidel-Bar, R., Itzkovitz, S., Ma'ayan, A. et al. Functional atlas of the integrin adhesome. Nat Cell Biol 9, 858–867 (2007). https://doi.org/10.1038/ncb0807-858

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncb0807-858

Further reading

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