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Integrin inactivators: balancing cellular functions in vitro and in vivo

Nature Reviews Molecular Cell Biology volume 14, pages 430–442 (2013)Cite this article

Subjects

Key Points

  • Correct integrin function requires constant switching of integrins between inactive and active conformations.

  • This switching is dynamically controlled by a multi-integrated system, including the interaction of integrins with inhibitory and activating proteins.

  • Interfering with integrin activity, both through integrin mutations or modulation of integrin inhibitors or activators, leads to strong phenotypes in mice and is linked to human pathologies.

Abstract

Integrins mediate cell–matrix and cell–cell interactions and integrate extracellular cues to the cytoskeleton and cellular signalling pathways. Integrin function on the cell surface is regulated by their activity switching such that intracellular proteins interacting with the integrin cytoplasmic domains increase or decrease integrin–ligand binding affinity. It is widely accepted that integrin activation by specific proteins is essential for cell adhesion and integrin linkage to the actin cytoskeleton. However, there is also increasing evidence that integrin-inactivating proteins are crucial for appropriate integrin function in vitro and in vivo and that the regulation of integrin–ligand interactions is a fine-tuned balancing act between inactivation and activation.

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Figure 1: Integrin inactivation.
Figure 2: The life of an integrin.

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Acknowledgements

J.I. has been supported by an European Research Council (ERC) starting grant, and funding from the Academy of Finland, the Sigrid Juselius foundation and the Finnish Cancer Organizations. J.P has been supported by the Cancer Society Finland and the Instrumentarium Foundation. D.B. is funded by INCa (Institut National du Cancer) grants.

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  1. Daniel Bouvard and Jeroen Pouwels: These authors contributed equally to this work.

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  1. Équipe 04 - Chromatine et épigenetique, Institut National de la Santé et de la Recherche Médicale U823, Institut Albert Bonniot, Grenoble, 38042, Cedex 09, France

    Daniel Bouvard

  2. VTT Medical Biotechnology and University of Turku, Centre for Biotechnology, Turku, FIN-20520, Finland

    Jeroen Pouwels, Nicola De Franceschi & Johanna Ivaska

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  1. Daniel Bouvard
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  2. Jeroen Pouwels
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  3. Nicola De Franceschi
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  4. Johanna Ivaska
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Correspondence to Johanna Ivaska.

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Supplementary information

Supplementary information S1 (table)

Phenotypes of integrin-knockout mice (PDF 151 kb)

Supplementary information S2 (table)

Phenotypes of mice lacking an integrin activator or inactivator (PDF 132 kb)

Supplementary information S3 (table)

Phenotypes of mice with mutated integrins and the effect of those mutations on integrin activity (PDF 111 kb)

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Bouvard, D., Pouwels, J., De Franceschi, N. et al. Integrin inactivators: balancing cellular functions in vitro and in vivo. Nat Rev Mol Cell Biol 14, 430–442 (2013). https://doi.org/10.1038/nrm3599

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