BACKGROUND: 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 á5â1 receptor, the relationship between fibronectin matrix assembly and the fate of internalized á5 integrin remains poorly characterized.MATERIALS AND METHODS: To evaluate the effect of fibronectin matrix on the fate of internalized á5 integrin, fibronectin-null Chinese hamster ovary and mouse embryo fibroblast cells were used to track the fate of á5 after exposure to exogenous fibronectin.RESULTS: In the absence of matrix-capable fibronectin dimer, levels of internalized á5 decreased rapidly over time. This correlated with a decline in total cellular á5 and was associated with the ubiquitination of á5 integrin. In contrast, internalized and total cellular á5 protein levels were maintained when matrix-capable fibronectin was present in the extracellular space. Further, we show that ubiquitination and degradation of internalized á5 integrin in the absence of fibronectin require the presence of two specific lysine residues in the á5 cytoplasmic tail.CONCLUSIONS: Our data demonstrate that á5 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.
Amino Acid Sequence Animals