- Integrins along with the cadherins, immunoglobulin superfamily and selectins comprise the four major groups of cell adhesion molecules.
- They are the major cell adhesion receptors in metazoans and are found in organisms ranging from sponges, corals, nematodes, and echinoderms to mammals.
- Integrins are a large family of type I transmembrane heterodimeric glycoprotein cell surface receptors, which are involved in cell – extracellular matrix (ECM) and cell – cell interactions.
- Integrins are catalytically inactive.
- They are composed of two distinct subunits; alpha (α) and beta (β) chains. These two subunits interact non-covalently, resulting in a heterodimeric integrin.
- Each heterodimer consists of a large extracellular domain which binds proteins in the extracellular environment, a single-membrane-spanning transmembrane domain, and a generally short intracellular cytoplasmic tail domain.
- So far eighteen α and eight β subunits have been identified in mammals which can assemble into 24 different integrins (αβ heterodimers). Specific integrin heterodimers preferentially bind to distinct ECM proteins.
- Both subunits are members of the single pass type-I transmembrane protein family.
- In active form, they can bind to ECM components, immunoglobulin superfamily molecules, soluble ligands, several divalent cations and other cells.
- Integrin activation may involve ligand binding, conformational changes and clustering.
- Integrins are involved in several biological functions including embryonic development and differentiation, tissue maintenance and repair, cell survival and proliferation, cell migration, homeostasis, immunity, etc. Dysfunctional integrins may lead to pathological conditions.
- Two modes of integrin signaling have been proposed.
- Outside-in signaling
- Inside-out signaling
- Outside-in signaling involves activation of integrins by ligand from cell microenvironment, whereas inside-out signaling requires activation factor from intracellular activators.
- Integrins have been shown to regulate as well as regulated by many signaling pathways including receptor tyrosine kinase pathway.
- Integrins act as transmembrane bridges between the ECM and actin filaments of the cytoskeleton.
- Aberrant integrin function may lead to development of many diseases including thrombosis, auto-immune diseases and cancer.
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