uPARAP/endo180 directs lysosomal delivery and degradation of collagen IV.

摘要: Collagen turnover is crucial for tissue homeostasis and remodeling pathological processes such as cancer invasion, but the underlying molecular mechanisms are poorly understood. A major pathway appears to be internalization degradation by fibroblasts. We now show that endocytic transmembrane glycoprotein urokinase plasminogen activator receptor-associated protein (uPARAP/endo180) directs collagen IV lysosomal delivery degradation. In wild-type fibroblasts, fluorescently labeled was first internalized into vesicular structures with diffuse fluorescence eventually appearing uniformly within cells after longer incubation times. these cells, some collagen-containing vesicles were identified lysosomes staining LAMP-1. contrast, remained extracellular associated fiber-like on uPARAP/endo180-deficient Blocking cysteine proteases inhibitor E64d resulted in strong accumulation of only very weak intracellular conclude uPARAP/endo180 critical targeted implicating receptor normal malignant matrix similar localization pattern observed V, suggesting might generally involved