| First Author | Kjøller L | Year | 2004 |
| Journal | Exp Cell Res | Volume | 293 |
| Issue | 1 | Pages | 106-16 |
| PubMed ID | 14729061 | Mgi Jnum | J:87760 |
| Mgi Id | MGI:3027659 | Doi | 10.1016/j.yexcr.2003.10.008 |
| Citation | Kjoller L, et al. (2004) uPARAP/endo180 directs lysosomal delivery and degradation of collagen IV. Exp Cell Res 293(1):106-16 |
| abstractText | Collagen turnover is crucial for tissue homeostasis and remodeling and pathological processes such as cancer invasion, but the underlying molecular mechanisms are poorly understood. A major pathway appears to be internalization and degradation by fibroblasts. We now show that the endocytic transmembrane glycoprotein urokinase plasminogen activator receptor-associated protein (uPARAP/endo180) directs collagen IV for lysosomal delivery and degradation. In wild-type fibroblasts, fluorescently labeled collagen IV was first internalized into vesicular structures with diffuse fluorescence eventually appearing uniformly within the wild-type cells after longer incubation times. In these cells, some collagen-containing vesicles were identified as lysosomes by staining for LAMP-1. In contrast, collagen IV remained extracellular and associated with fiber-like structures on uPARAP/endo180-deficient fibroblasts. Blocking lysosomal cysteine proteases with the inhibitor E64d resulted in strong accumulation of collagen IV in lysosomes in wild-type cells, but only very weak intracellular fluorescence accumulation in uPARAP/endo180-deficient fibroblasts. We conclude that uPARAP/endo180 is critical for targeted delivery of collagen IV to lysosomes for degradation implicating the receptor in normal and malignant extracellular matrix degradation. A similar localization pattern was observed for collagen V, suggesting that uPARAP/endo180 might be generally involved in collagen degradation. |
