Interactions between the discoidin domain receptor 1 and β1 integrin regulate attachment to collagen.
Biology Open, January 2013
Lisa A Staudinger, Stephen J Spano, Wilson Lee, Nuno Coelho, Dhaarmini Rajshankar, Michelle P Bendeck, Tara Moriarty, Christopher A McCulloch, Staudinger LA, Spano SJ, Lee W, Coelho N, Rajshankar D, Bendeck MP, Moriarty T, McCulloch CA, Lisa A. Staudinger, Stephen J. Spano, Michelle P. Bendeck, Christopher A. McCulloch
Collagen degradation by phagocytosis is essential for physiological collagen turnover and connective tissue homeostasis. The rate limiting step of phagocytosis is the binding of specific adhesion receptors, which include the integrins and discoidin domain receptors (DDR), to fibrillar collagen. While previous data suggest that these two receptors interact, the functional nature of these interactions is not defined. In mouse and human fibroblasts we examined the effects of DDR1 knockdown and over-expression on β1 integrin subunit function. DDR1 expression levels were positively associated with enhanced contraction of floating and attached collagen gels, increased collagen binding and increased collagen remodeling. In DDR1 over-expressing cells compared with control cells, there were increased numbers, area and length of focal adhesions immunostained for talin, paxillin, vinculin and activated β1 integrin. After treatment with the integrin-cleaving protease jararhagin, in comparison to controls, DDR1 over-expressing cells exhibited increased β1 integrin cleavage at the cell membrane, indicating that DDR1 over-expression affected the access and susceptibility of cell-surface β1 integrin to the protease. DDR1 over-expression was associated with increased glycosylation of the β1 integrin subunit, which when blocked by deoxymannojirimycin, reduced collagen binding. Collectively these data indicate that DDR1 regulates β1 integrin interactions with fibrillar collagen, which positively impacts the binding step of collagen phagocytosis and collagen remodeling.
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