Role of the I-domain in collagen binding specificity and activation of the integrins alpha1beta1 and alpha2beta1.
Adhesion to collagens by most cell types is mediated by the integrins alpha1beta1 and alpha2beta1. Both integrin alpha subunits belong to a group which is characterized by the presence of an I domain in the N-terminal half of the molecule, and this domain has been implicated in the ligand recognition. Since purified alpha1beta1 and alpha2beta1 differ in their binding to collagens I and IV and recognize different sites within the major cell binding domain of collagen IV, we investigated the potential role of the alpha1 and alpha2 I domains in specific collagen adhesion. We find that introducing the alpha2 I domain into alpha1 results in surface expression of a functional collagen receptor. The adhesion mediated by this chimeric receptor (alpha1-2-1beta1) is similar to the adhesion profile conferred by alpha2beta1, not alpha1beta1. The presence of alpha2 or alpha1-2-1 results in preferential binding to collagen I, whereas alpha1 expressing cells bind better to collagen IV. In addition, alpha1 containing cells bind to low amounts of a tryptic fragment of collagen IV, whereas alpha2 or alpha1-2-1 bearing cells adhere only to high concentrations of this substrate. We also find that collagen adhesion of NIH-3T3 mediated by alpha2beta1 or alpha1-2-1beta1, but not by alpha1, requires the presence of Mn2+ ions. This ion requirement was not found in CHO cells, implicating the I domain in cell type-specific activation of integrins.
Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
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Kern
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Marcantonio
D016475:3T3 Cells / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D000818:Animals; D016375:Antisense Elements (Genetics); D016466:CHO Cells / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D003094:Collagen / Q000378:metabolism*; D006224:Cricetinae; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D039222:Integrin alpha1beta1; D016023:Integrins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology; D051379:Mice; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D017434:Protein Structure, Tertiary; D038981:Receptors, Collagen; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D016375:Antisense Elements (Genetics); D039222:Integrin alpha1beta1; D016023:Integrins; D010446:Peptide Fragments; D038981:Receptors, Collagen; D011993:Recombinant Fusion Proteins; D003094:Collagen; D008274:Magnesium