Kern A, Marcantonio E E
Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
J Cell Physiol. 1998 Sep;176(3):634-41. doi: 10.1002/(SICI)1097-4652(199809)176:3<634::AID-JCP20>3.0.CO;2-Y.
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.
大多数细胞类型与胶原蛋白的黏附是由整合素α1β1和α2β1介导的。这两种整合素α亚基都属于一个分子组，其特征是在分子的N端一半存在一个I结构域，并且该结构域与配体识别有关。由于纯化的α1β1和α2β1在与I型和IV型胶原蛋白的结合上存在差异，并且识别胶原蛋白IV主要细胞结合域内的不同位点，我们研究了α1和α2 I结构域在特定胶原蛋白黏附中的潜在作用。我们发现将α2 I结构域引入α1会导致功能性胶原蛋白受体的表面表达。由这种嵌合受体（α1-2-1β1）介导的黏附类似于α2β1而非α1β1赋予的黏附模式。α2或α1-2-1的存在导致优先与I型胶原蛋白结合，而表达α1的细胞与IV型胶原蛋白结合得更好。此外，含有α1的细胞与少量的胶原蛋白IV胰蛋白酶片段结合，而含有α2或α1-2-1的细胞仅黏附于该底物的高浓度形式。我们还发现由α2β1或α1-2-1β1介导的NIH-3T3细胞与胶原蛋白的黏附需要Mn2+离子的存在，而α1介导的黏附则不需要。在CHO细胞中未发现这种离子需求，这表明I结构域参与了整合素的细胞类型特异性激活。
