Cell adhesion to the extracellular matrix (ECM) is crucial for determining cell fate, cell proliferation and cell migration and is mediated primarily by a family of cell surface receptors called integrins.
Integrins form 24 distinct heterodimers composed of an α and a β subunit with large extracellular domains and predominantly short cytoplasmic tails. The specific subunit pairing dictates ligand specificity and determines the precise cellular response.
Integrins, through direct binding to ECM molecules, provide a physical link between the cell cytoskeleton and the surrounding environment and act as a signalling nexus by recruiting adaptor and signalling proteins to their cytoplasmic domains.
Tight control over integrin signalling is paramount for normal cell function and occurs through regulation of integrin activity, modulation of integrin trafficking pathways (i.e. endocytosis, degradation and recycling) and through receptor crosstalk (e.g. integrins and RTKs).
Misregulation of pathways that would normally confer tight control over integrin activity or RTK signalling is linked to anchorage-independent cell growth, increased cell migration, the onset of cancer cell invasion and several other diseases.
Integrins, heterodimeric cell-surface receptors for ECM proteins, are composed of an α and a β subunit. Here, a very simplified version of the α-β-subunit pairing and the major extracellular ligands for each heterodimer is represented. N.B. The same integrin receptor can bind to several different ECM ligands. Intriguingly, the engagement of different integrins by the same matrix molecule can elicit very different cellular responses.