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.
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References
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).
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).
Critchley, D. R. et al. Integrin-mediated cell adhesion: the cytoskeletal connection. Biochem. Soc. Symp. 65, 79–99 (1999).
Geiger, B. & Bershadsky, A. Exploring the neighborhood: adhesion-coupled cell mechanosensors. Cell 110, 139–142 (2002).
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).
Cukierman, E., Pankov, R., Stevens, D. R. & Yamada, K. M. Taking cell-matrix adhesions to the third dimension. Science 294, 1708–1712 (2001).
Humphries, M. J. The molecular basis and specificity of integrin-ligand interactions. J. Cell Sci. 97, 585–592 (1990).
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).
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).
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).
Brown, M. C. & Turner, C. E. Paxillin: adapting to change. Physiol. Rev. 84, 1315–1339 (2004).
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).
Lo, S. H. Focal adhesions: what's new inside. Dev. Biol. 294, 280–291 (2006).
Zamir, E. & Geiger, B. Molecular complexity and dynamics of cell-matrix adhesions. J. Cell Sci. 114, 3583–3590 (2001).
Zamir, E. & Geiger, B. Components of cell-matrix adhesions. J. Cell Sci. 114, 3577–3579 (2001).
Bader, G. D., Betel, D. & Hogue, C. W. BIND: the Biomolecular Interaction Network Database. Nucleic Acids Res. 31, 248–250 (2003).
Mishra, G. R. et al. Human protein reference database — 2006 update. Nucleic Acids Res. 34, D411–D414 (2006).
Shannon, P. et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 13, 2498–2504 (2003).
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).
Iragne, F., Nikolski, M., Mathieu, B., Auber, D. & Sherman, D. ProViz: protein interaction visualization and exploration. Bioinformatics 21, 272–274 (2005).
Zanzoni, A. et al. MINT: a Molecular INTeraction database. FEBS Lett. 513, 135–140 (2002).
Xenarios, I. et al. DIP: the database of interacting proteins. Nucleic Acids Res. 28, 289–291 (2000).
Rual, J. F. et al. Towards a proteome-scale map of the human protein-protein interaction network. Nature 437, 1173–1178 (2005).
Stelzl, U. et al. A human protein-protein interaction network: a resource for annotating the proteome. Cell 122, 957–968 (2005).
Watts, D. J. & Strogatz, S. H. Collective dynamics of 'small-world' networks. Nature 393, 440–442 (1998).
Caldarelli, G., Pastor-Satorras, R. & Vespignani, A. Structure of cycles and local ordering in complex networks. Eur. Phys. J. B 38, 183–186 (2004).
Jeong, H., Mason, S. P., Barabasi, A. L. & Oltvai, Z. N. Lethality and centrality in protein networks. Nature 411, 41–42 (2001).
Albert, R., Jeong, H. & Barabasi, A. L. Error and attack tolerance of complex networks. Nature 406, 378–382 (2000).
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).
Parsons, S. J. & Parsons, J. T. Src family kinases, key regulators of signal transduction. Oncogene 23, 7906–7909 (2004).
Gough, N. R. & Ray, L. B. Mapping cellular signaling. Sci STKE 135, EG8 (2002).
Ma'ayan, A., Blitzer, R. D. & Iyengar, R. Toward predictive models of mammalian cells. Annu. Rev. Biophys. Biomol. Struct. 34, 319–349 (2005).
Mostafavi-Pour, Z. et al. Integrin-specific signaling pathways controlling focal adhesion formation and cell migration. J. Cell Biol. 161, 155–167 (2003).
Mangan, S. & Alon, U. Structure and function of the feed-forward loop network motif. Proc. Natl Acad. Sci. USA 100, 11980–11985 (2003).
Alon, U. Biological networks: the tinkerer as an engineer. Science 301, 1866–1867 (2003).
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).
Milo, R. et al. Network motifs: simple building blocks of complex networks. Science 298, 824–827 (2002).
Kashtan, N., Itzkovitz, S., Milo, R. & Alon, U. Efficient sampling algorithm for estimating subgraph concentrations and detecting network motifs. Bioinformatics 20, 1746–1758 (2004).
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.
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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
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DOI: https://doi.org/10.1038/ncb0807-858
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