Integrin Superfamily


Integrins are cell‐surface adhesion molecules formed from eight different β chains and 18 different α chains that assemble as heterodimeric transmembrane receptors to mediate cell–cell and cell–matrix interactions. The integrin superfamily first emerged in the metazoa and has expanded with evolution creating 24 different integrins in humans, each recognising a distinct subset of extracellular ligands. Ligands include extracellular matrix proteins found in basement membranes such as laminins or in fibrilar matrices such as collagen or fibronectin meshworks, as well as counter receptors on neighbouring cells. The adhesive potential of integrins can be regulated and their cytoplasmic tails connect through a dynamic protein interaction network to the cytoskeleton. Thus, integrins provide cells with the capacity to sense and respond to their microenvironment and they control vital cellular functions for embryonic development, tissue homoeostasis, blood clotting and immunity.

Key Concepts:

  • Integrins are heterodimeric transmembrane receptors that mediate cell adhesion to the microenvironment.

  • More than 600 Mya integrins emerged and the integrin superfamily has expanded throughout evolution.

  • In humans, 24 different integrins are formed from 18 α and 8 β subunits.

  • Integrins recognise a wide range of ligands, including extracellular matrix proteins, counter receptors on neighbouring cells, plasma proteins, and microbes and viruses.

  • Integrins couple the extracellular microenvironment to the cytoskeleton through a protein interaction network associated with their cytoplasmic tails.

Keywords: integrin; cell adhesion; extracellular matrix; matrix; receptor; conformation; activation; gene knockout studies

Figure 1.

Structural features of integrins. Schematic illustrations of the structural features of (a) non‐I‐domain and (b) I‐domain integrins. Both I‐domain α‐subunits and N‐terminal regions of β‐subunits contain a metal‐ion‐dependent adhesion site (MIDAS) motif involved in ligand binding. β‐propeller repeats 5–7 of I‐domain α‐subunits, and repeats 4–7 of non‐I‐domain α‐subunits contain EF‐hand‐like cation‐binding sequences that bind Ca2+ and negatively regulate ligand binding. A β‐turn in the third β‐propeller repeat involved in ligand binding by α subunits is denoted by an asterisk. Integrin β subunits contain four repeats of an eight cysteine motif resembling EGF‐like motifs.

Figure 2.

Integrin subunit pairings. There are 18 α‐ and 8 β‐integrin subunits from which 24 different functional integrins are currently known to be formed.



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Further Reading

Danen EHJ (2005) Integrins and Development. Georgetown, TX: Landes Bioscience. ISBN: 978‐1‐58706‐293‐3.

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Hynes RO and Naba A (2012) Overview of the matrisome – an inventory of extracellular matrix constituents and functions. Cold Spring Harbor Perspectives in Biology 4(1): 1–16.

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Danen, Erik HJ(Sep 2013) Integrin Superfamily. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0000927.pub3]