The fate of internalized α5 integrin is regulated by matrix-capable fibronectin.

Assembly of fibronectin matrices is associated with integrin receptor turnover and is an important determinant of tissue remodeling. Although it is well established that fibronectin is the primary ligand for α5β1 receptor, the relationship between fibronectin matrix assembly and the fate of internalized α5 integrin remains poorly characterized.To evaluate the effect of fibronectin matrix on the fate of internalized α5 integrin, fibronectin-null Chinese hamster ovary and mouse embryo fibroblast cells were used to track the fate of α5 after exposure to exogenous fibronectin.In the absence of matrix-capable fibronectin dimer, levels of internalized α5 decreased rapidly over time. This correlated with a decline in total cellular α5 and was associated with the ubiquitination of α5 integrin. In contrast, internalized and total cellular α5 protein levels were maintained when matrix-capable fibronectin was present in the extracellular space. Further, we show that ubiquitination and degradation of internalized α5 integrin in the absence of fibronectin require the presence of two specific lysine residues in the α5 cytoplasmic tail.Our data demonstrate that α5 integrin turnover is dependent on fibronectin matrix assembly, where the absence of matrix-capable fibronectin in the extracellular space targets the internalized receptor for rapid degradation. These findings have important implications for understanding tissue-remodeling processes found in wound repair and tumor invasion.