The fate of internalized ?5 integrin is regulated by matrix-capable fibronectin.

ABSTRACT: 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 ?5?1 receptor, the relationship between fibronectin matrix assembly and the fate of internalized ?5 integrin remains poorly characterized.To evaluate the effect of fibronectin matrix on the fate of internalized ?5 integrin, fibronectin-null Chinese hamster ovary and mouse embryo fibroblast cells were used to track the fate of ?5 after exposure to exogenous fibronectin.In the absence of matrix-capable fibronectin dimer, levels of internalized ?5 decreased rapidly over time. This correlated with a decline in total cellular ?5 and was associated with the ubiquitination of ?5 integrin. In contrast, internalized and total cellular ?5 protein levels were maintained when matrix-capable fibronectin was present in the extracellular space. Further, we show that ubiquitination and degradation of internalized ?5 integrin in the absence of fibronectin require the presence of two specific lysine residues in the ?5 cytoplasmic tail.Our data demonstrate that ?5 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.

SUBMITTER: Hsia HC 

PROVIDER: S-EPMC4160403 | biostudies-other | 2014 Oct

REPOSITORIES: biostudies-other