Integrin alpha2

Abstract: The α2β1 integrin is a collagen/laminin receptor expressed on platelets, endothelial cells, fibroblasts, and epithelial cells To define the role of the α2β1 integrin in vivo, we created a genetically engineered mouse in which expression of the α2β1 integrin was completely eliminated Mice deficient in the α2β1 integrin are viable, fertile, and develop normally with no excess lethality of homozygotes Both α2β1-integrin protein and α2 mRNA were undetectable in the α2-null mice Gross and histological evaluation of the heart, lungs, kidneys, gastrointestinal tract, pancreas, skin, and reproductive tracts revealed no abnormalities However, quantitative analysis of mammary gland branching morphogenesis demonstrated that branching complexity is markedly diminished in the α2-deficient animals Studies in the α2-deficient animals do not support the proposed roles for the α2β1 integrin on fibroblasts and keratinocytes in wound healing When compared to platelets from wild-type littermates, platelets from α2-null mice failed to adhere to type I collagen under either static or shear-stress conditions Although platelets from α2-deficient animals aggregated in response to collagen, they did so with prolonged lag time and lessened intensity The α2β1 integrin-null mouse thus exhibits diverse, sometimes subtle, phenotypes consistent with the widespread pattern of α2β1 integrin expression

Abstract: Integrins alpha 1 beta 1 and alpha 2 beta 1 are major cellular receptors for collagens. The alpha 1 and alpha 2 subunits contain a approximately 200 amino acid inserted domain (I-domain) in their N-terminal region and, because of the homology between the I-domains and the collagen-binding A-domains of von Willebrand factor, it has been suggested that the I-domains might mediate the collagen-binding functions of alpha 1 beta 1 and alpha 2 beta 1. In order to fully investigate this hypothesis, we have generated recombinant human alpha 2 I-domain (r alpha 2I) by reverse transcriptase-polymerase chain reaction/bacterial expression and tested its ability to mediate the collagen-binding functions of alpha 2 beta 1. R alpha 2 I binds specifically to type I collagen in a concentration-dependent manner: binding is cation dependent and, like the complete receptor, is supported by magnesium and manganese ions but not by calcium ions. R alpha 2I is recognised by anti-functional anti-alpha 2 monoclonal antibodies 6F1, 5E8 and P1E6 in capture ELISAs, and anti-functional antibodies inhibited r alpha 2I-collagen binding. In addition, r alpha 2I inhibits cell spreading on collagen. R alpha 2I is therefore a collagen-binding domain and can account for many of the collagen-binding functions of integrin alpha 2 beta 1. We have also determined the collagen specificity of r alpha 2I and found that it binds types I, II and XI collagen.