Martin Humphries, BSc PhD FMedSci
Integrins as molecules
Integrins are cell-surface adhesion receptors. They have large extracellular domains, single-pass transmembrane regions and short cytoplasmic domains. The extracellular “heads” of integrins bind to proteins of the extracellular matrix or to counter-receptors on other cells; the cytoplasmic “tails” are able to link to the actin cytoskeleton. Integrins are able to transduce signals in both directions across the cell membrane, thus integrating the intracellular and extracellular environments. This provides a means for cells to sense their environment and to modulate and co-ordinate essential aspects of cell behaviour crucial to the development and maintenance of organisms.
Adhesion signalling complexes are molecularly diverse structures that associate with integrins to enable proper cell adhesion. We have developed a methodology for the affinity isolation and mass spectrometric analysis of integrin-associated complexes. Importantly, the technique isolates stabilised, ligand-engaged integrin adhesion complexes and fractionates the cell to permit the enrichment of insoluble integrin-associated cytoskeletal components. This approach has enabled us to describe the first ligand-induced integrin proteomes.
Integrin and syndecan signalling
Cell migration during developmental, repair and disease processes is critically dependent on interaction with the extracellular matrix (ECM). Focal adhesions are dynamic sites of contact at the cell-ECM interface that serve as points of integration between the ECM and cytoskeleton and as coordinating nexuses of signalling events. Precise spatiotemporal control of focal adhesion dynamics is essential to permit efficient cell migration, regulating both locomotive cellular traction and the signals that dictate directionality.
Integrin extracellular domains bind to either ECM macromolecules or counter-receptors on adjacent cell surfaces. Most integrin receptors can bind a wide variety of ligands. Moreover, many ECM and cell adhesion proteins can bind to multiple integrin receptors.
Changes in integrin shape regulate its activation state. Monoclonal antibodies that detect conformation-dependent integrin epitopes have been produced. These antibodies enable the study of dynamic conformational changes of integrin.
Tel: +44 (0) 161 275 5071
Recent key publications
Morgan, M.R., Hamidi, H., Bass, M.D., Warwood, S., Ballestrem C. and Humphries, M.J. (2013). Syndecan-4 phosphorylation is a control point for integrin recycling. Dev Cell. 24, 472-85. Dev Cell
Bass, M.D., Williamson, R.C., Humphries, J.D., Byron, A., Morgan, M.R., Martin P. and Humphries, M.J. (2011). A syndecan-4 hair trigger initiates wound healing through caveolin- and RhoG-regulated integrin endocytosis. Dev. Cell 21, 681-93. PubMed
Askari, J.A., Tynan, C.J., Webb, S.E., Martin-Fernandez, M.L., Ballestrem, C., and Humphries, M.J. (2010) Focal adhesions are sites of integrin extension. J Cell Biol. 188, 891-903 PubMed.