Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

uPARAP/endo180 directs lysosomal delivery and degradation of collagen IV

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Human myotubularin-related protein 9 regulates ER-to-Golgi trafficking and modulates WNT3A secretion

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. A programmed wave of uridylation-primed mRNA degradation is essential for meiotic progression and mammalian spermatogenesis

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Hepatitis B virus upregulates host microRNAs that target apoptosis-regulatory genes in an in vitro cell model

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Personalized B cell response to the Lactobacillus rhamnosus GG probiotic in healthy human subjects: a randomized trial

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Tumor cell MT1-MMP is dispensable for osteosarcoma tumor growth, bone degradation and lung metastasis

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. The collagen receptor uPARAP/Endo180 regulates collectins through unique structural elements in its FNII domain

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Cellular uptake of collagens and implications for immune cell regulation in disease

    Research output: Contribution to journalReviewResearchpeer-review

  5. TAFI deficiency causes maladaptive vascular remodeling after hemophilic joint bleeding

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

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.

Original languageEnglish
JournalExperimental Cell Research
Volume293
Issue number1
Pages (from-to)106-16
Number of pages11
ISSN0014-4827
Publication statusPublished - 1 Feb 2004

    Research areas

  • Animals, Animals, Newborn, Antibodies, Monoclonal, Antigens, CD, Cells, Cultured, Collagen Type IV, Cysteine Endopeptidases, Enzyme Inhibitors, Fibroblasts, Kinetics, Leucine, Lysosome-Associated Membrane Glycoproteins, Lysosomes, Membrane Glycoproteins, Mice, Mice, Knockout, Rats, Receptors, Cell Surface, Skin, Subcellular Fractions

ID: 46435647