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Integrins: Signalling and Disease

  1. Erik HJ Danen

Published Online: 20 SEP 2013

DOI: 10.1002/9780470015902.a0004022.pub3

eLS

eLS

How to Cite

Danen, E. H. 2013. Integrins: Signalling and Disease. eLS. .

Author Information

  1. Leiden University, Division of Toxicology, LACDR, Leiden, The Netherlands

  1. Based in part on the previous version of this eLS article ‘Integrins: Signalling and Disease’ (2006) by Geoffrey W Krissansen and Erik HJ Danen.

Publication History

  1. Published Online: 20 SEP 2013

Abstract

Abstract

Cell-surface adhesion molecules of the integrin family are not a passive glue, but rather are dynamic molecules that mediate the transfer of information across the membrane in both directions. Integrin-mediated adhesion can be regulated in response to signals by clustering and conformational changes triggered at their cytoplasmic tails. Vice versa, integrins probe chemical and physical aspects of the extracellular environment and, in concert with growth factor receptors, activate signalling pathways in response. Integrin signalling controls cell survival, cell cycle progression, and differentiation, and the dynamic regulation of integrin-mediated adhesion structures is critical for many forms of cell migration. Lastly, integrins contribute to the pathogenesis of a diverse array of acquired and hereditary diseases, and hence represent major targets for therapeutic intervention.

Key Concepts:

  • Integrins are heterodimeric transmembrane receptors that mediate cell adhesion to extracellular matrix proteins and other cells.

  • Integrins cluster in cell–matrix or cell–cell adhesions where they assemble large multiprotein complexes including actin-binding proteins.

  • Integrin-containing adhesions contain enzymes such as FAK, Src, Rac and many others as well as their upstream activators and downstream effectors allowing local activation of cellular signalling cascades.

  • Through a series of conformational changes in mechanoresponsive proteins, integrin-containing adhesions provide mechanical coupling between the environment and the cytoskeletal network.

  • Signalling through various growth factor receptors is amplified in response to integrin-mediated adhesion.

  • The ability of integrins to modulate cellular shape and cytoarchitecture in accordance with environmental stiffness as well as their role in a variety of biochemical signal transduction cascades underlies their critical function in cell proliferation, survival, differentiation and motility.

  • Defective integrin function underlies several human diseases.

  • Integrins represent potential drug targets and therapeutic strategies based on interference with integrin-mediated adhesion have entered clinical trials.

Keywords:

  • integrin;
  • cell adhesion;
  • signalling;
  • disease