| The alpha1beta1 integrin belongs to a family of cell surface molecules involved in structural contacts and signal transduction events across the cell membrane. Previous studies have shown that this collagen binding integrin, unlike several others, associates with the adapter protein Shc and transmits signals to the Ras/MAPK signal transduction pathway resulting in growth and proliferation. NIH 3T3 fibroblasts were stably expressing the alpha1beta1 and non Shc-associated alpha2beta1 integrin to support these earlier and subsequent studies.; The collagen matrix surrounding cardiac myocytes is altered in cardiac hypertrophy. I tried to link either the particular signaling of alpha1beta1 or its putative interaction with a collagen degrading matrix metalloprotease (MMP-1) to this alteration. To answer this, the effects of the deletion of the alpha1beta1 integrin were examined in a transgenic mouse model of disease in which a MMP-1 was overexpressed in the heart. Some component of the genetic background of the mice nullified the original heart failure phenotype. Future work in backcrossing these animals to a homogeneous genetic background may prove fruitful.; Employing two dimensional substrates coated with fluorescently labeled type I collagen, this work characterizes a novel subcellular matrix remodeling event that is particular to cells which express the fibrillar collagen receptor alpha2beta1. Cells expressing alpha1beta1 also perform this collagen organization process, but less proficiently. This process occurs independently of MMP activity as inhibitors to MMPs fail to stop this process. This work will prove valuable to studies of cell mediated collagen fibril assembly. |
