Integrins are cell-surface receptors that mediate and coordinate cellular responses to the extracellular matrix. Cellular signalling pathways can regulate cell adhesion by altering the affinity and avidity of integrins for the extracellular matrix.

Function

Integrins are a large family of transmembrane receptors for extracellular matrix (ECM) molecules. They play a critical role in organ morphogenesis, physiology and pathology, as they can modulate and control different cell functions, including cell adhesion, cell shape, cell polarity, cell growth, cell differentiation and cell motility.

Integrins interact with ECM components via their extracellular domains, while their cytoplasmic domains play a pivotal role in mediating integrin-dependent cellular functions.

The integrin cytoplasmic tails interact with the cytoskeleton, signaling molecules and other cellular proteins, resulting in regulation of many biological functions.

Subtypes

 PS integrins

Features

 spatial pattern of integrins

Functional synopsis

 cell adhesion
 signaling
 morphogenesis

Pathology (integrin-dependent pathologies)

 leucocyte adhesion deficiency type 1 (LAD-1) : mutations of beta2-integrins (Deletion or reduced cell surface expression)

 Glanzmann thrombasthenia (GT) : mutations in alpahIIb and beta3-Integrins (deletions; point mutations in ligand binding site, stem and cytoplasmic tail)

 Glanzmann thrombasthenia : beta3-Integrins (Integrin locked in high affinity config (C560R))

 thrombosis : beta3-Integrins L33/P33 polymorphism; risc for thrombosis

 epidermolysis bullosa : beta6-integrins (Splicing defect in exon 12 (1856 + 1GtoT))

 epidermolysis bullosa 4-integrins missense and premature stop, cytoplasmic deletion

 Oral pemphigoid : alpha6-Integrins (Autoantibodies against alpha6 integrin)

 Congenital myopathy: alpha7-Integrins (Missense, internal insertions and deletions)

 Squamous cell carcinoma (SCC4): beta1-Integrins (Integrin activation, point mutation T188I in the ligand binding domain)

Features

 cancer cell invasion
 cancer cell migration

References

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 Rhee JS, Santoso S, Herrmann M, Bierhaus A, Kanse SM, May AE, Nawroth PP, Colman RW, Preissner KT, Chavakis T. New aspects of integrin-mediated leukocyte adhesion in inflammation: regulation by haemostatic factors and bacterial products. Curr Mol Med. 2003 Jun;3(4):387-92. PMID: #12776993#

 Isberg RR, Van Nhieu GT. The mechanism of phagocytic uptake promoted by invasin-integrin interaction. Trends Cell Biol. 1995 Mar;5(3):120-4. PMID: #14732167#

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 Hood JD, Cheresh DA. Role of integrins in cell invasion and migration. Nat Rev Cancer. 2002 Feb;2(2):91-100. PMID: #12635172#

 De Arcangelis A, Georges-Labouesse E. Integrin and ECM functions: roles in vertebrate development. Trends Genet. 2000 Sep;16(9):389-95. PMID: #10973067#

 Beauvais-Jouneau A, Thiery JP. Multiple roles for integrins during development. Biol Cell. 1997 Mar;89(1):5-11. PMID: #9297778#