The International Journal of Biochemistry & Cell Biology
Molecules in focusThe collagen receptor subfamily of the integrins
Introduction
Integrins are receptors mediating cell adhesion to extracellular matrix (ECM). Integrins consist of one α and one β subunit forming a noncovalently bound heterodimer (Hynes, 2002). Eight β and 18 α subunits exist in man, forming twenty four different heterodimers. Laminin receptor integrins, as well as fibronectin and vitronectin receptor integrins recognising proteins with the Arg-Gly-Asp (RGD) motif or other similar motifs, are expressed in all Metazoans. Integrins that have an additional inserted domain (αI-domain) in their α subunit are only found in Chordates, including vertebrates, not in Nematodes or Arthropods. Four out of the nine αI containing integrins, namely α1β1, α2β1, α10β1 and α11β1, are receptors for collagens, the most abundant ECM proteins.
Section snippets
Structure
Recently, crystal structures of the ectodomain of the fibronectin receptor integrin αVβ3 have been solved with and without a peptide ligand mimicking the RGD motif (Xiong et al., 2001). The αV subunit contains no αI, however several crystal structures of integrin αI domains are available representing the active α2I and inactive α2I (Emsley, Knight, Farndale, Barnes, & Liddington, 2000) and α1I (Salminen et al., 1999). NMR structures are now available for the I-EFG3 domain from β2 which is
Synthesis and degradation
In man, all four collagen receptor integrins have different expression patterns. Integrin α1β1 is expressed in mesenchymal cell types including smooth muscle cells, endothelial cells, fibroblasts and chondrocytes (Voigt et al., 1995). It is also found on certain lymphocytes and monocytes. Integrin α2β1 is expressed on epithelial cells, platelets, endothelial cells, fibroblasts, chondrocytes (Zutter & Santoro, 1990), lymphocytes, mast cells, and neutrophilic granulocytes. The expression pattern
Biological function
The structures of the collagen binding αI-domains, α1I, α2I, α10I and α11I, are very similar. However, αI-domain binding assays indicate differences in their ligand binding mechanisms and their collagen subtype specificity (Tulla et al., 2001, Zhang et al., 2003). Characteristically, α1β1 prefers basement membrane type IV collagen over fibril forming collagens, opposite to the α2β1 preference (Kern, Eble, Golbik, & Kuhn, 1993). Also, α1β1 is a receptor for beaded filaments forming type VI
Possible medical and industrial application
Human epidemiological studies indicate that high α2β1 integrin platelet surface levels increase the risk of cerebrovascular stroke and myocardial infarction (Moshfegh et al., 1999). Furthermore, α2β1 is expressed on variable cancer cell types, including melanoma. These observations present α2β1 integrin as an exciting drug target.
References (26)
- et al.
Does the integrin alphaA domain act as a ligand for its betaA domain?
Current Biology
(2002) - et al.
The alpha(2) integrin subunit-deficient mouse: A multifaceted phenotype including defects of branching morphogenesis and hemostasis
American Journal of Pathology
(2002) - et al.
Diminished callus size and cartilage synthesis in alpha 1 beta 1 integrin-deficient mice during bone fracture healing
American Journal of Pathology
(2002) - et al.
Structural basis of collagen recognition by integrin alpha2beta1
Cell
(2000) - et al.
Importance of innate immunity and collagen binding integrin alpha1beta1 in TNBS-induced colitis
Immunity
(2002) The collagen receptor integrins have distinct ligand recognition and signaling functions
Matrix Biology
(2000)Integrins: Bi-directional, allosteric signaling machines
Cell
(2002)- et al.
Association of two silent polymorphisms of platelet glycoprotein Ia/IIa receptor with risk of myocardial infarction: A case–control study
Lancet
(1999) - et al.
Alpha11beta1 integrin is a receptor for interstitial collagens involved in cell migration and collagen reorganization on mesenchymal nonmuscle cells
Developmental Biology
(2001) - et al.
Selective binding of collagen subtypes by integrin alpha 1I, alpha 2I, and alpha 10I domains
Journal of Biological Chemistry
(2001)
alpha11 beta1 integrin recognizes the GFOGER sequence in interstitial collagens
Journal of Biological Chemistry
Cysteine-rich module structure reveals a fulcrum for integrin rearrangement upon activation
Nature Structural Biology
Distribution of the collagen-binding integrin alpha10beta1 during mouse development
Cell Tissue Research
Cited by (151)
The α<inf>1</inf> integrin cytoplasmic tail interacts with phosphoinositides and interferes with Akt activation
2024, Biochimica et Biophysica Acta - BiomembranesBiomaterial control of adipose-derived stem/stromal cell differentiation
2021, Scientific Principles of Adipose Stem Cells