A novel functional role of collagen glycosylation: Interaction with the endocytic collagen receptor uPARAP/ENDO180

Henrik J. Jürgensen, Daniel H. Madsen, Signe Ingvarsen, Maria C. Melander, Henrik Gårdsvoll, L. Patthy, Lars H. Engelholm, Niels Behrendt

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Collagens make up the most abundant component of interstitial extracellular matrices and basement membranes. Collagen remodeling is a crucial process in many normal physiological events and in several pathological conditions. Some collagen subtypes contain specific carbohydrate side chains, the function of which is poorly known. The endocytic collagen receptor urokinase plasminogen activator receptor-associated protein (uPARAP)/Endo180 plays an important role in matrix remodeling through its ability to internalize collagen for lysosomal degradation. uPARAP/Endo180 is a member of the mannose receptor protein family. These proteins all include a fibronectin type II domain and a series of C-type lectin-like domains, of which only a minor part possess carbohydrate recognition activity. At least two of the family members, uPARAP/Endo180 and the mannose receptor, interact with collagens. The molecular basis for this interaction is known to involve the fibronectin type II domain but nothing is known about the function of the lectin domains in this respect. In this study, we have investigated a possible role of the single active lectin domain of uPARAP/Endo180 in the interaction with collagens. By expressing truncated recombinant uPARAP/Endo180 proteins and analyzing their interaction with collagens with high and low levels of glycosylation we demonstrated that this lectin domain interacts directly with glycosylated collagens. This interaction is functionally important because it was found to modulate the endocytic efficiency of the receptor toward highly glycosylated collagens such as basement membrane collagen IV. Surprisingly, this property was not shared by the mannose receptor, which internalized glycosylated collagens independently of its lectin function. This role of modulating its uptake efficiency by a specific receptor is a previously unrecognized function of collagen glycosylation.

Original languageEnglish
Pages (from-to)32736-32748
Number of pages13
JournalJournal of Biological Chemistry
Volume286
Issue number37
DOIs
Publication statusPublished - Sep 16 2011

Fingerprint

Collagen Receptors
Urokinase Plasminogen Activator Receptors
Glycosylation
Collagen
Lectins
Proteins
Fibronectins
Basement Membrane
Carbohydrates
C-Type Lectins
Efficiency
Aptitude
Extracellular Matrix
Endo180

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Jürgensen, H. J., Madsen, D. H., Ingvarsen, S., Melander, M. C., Gårdsvoll, H., Patthy, L., ... Behrendt, N. (2011). A novel functional role of collagen glycosylation: Interaction with the endocytic collagen receptor uPARAP/ENDO180. Journal of Biological Chemistry, 286(37), 32736-32748. https://doi.org/10.1074/jbc.M111.266692

A novel functional role of collagen glycosylation : Interaction with the endocytic collagen receptor uPARAP/ENDO180. / Jürgensen, Henrik J.; Madsen, Daniel H.; Ingvarsen, Signe; Melander, Maria C.; Gårdsvoll, Henrik; Patthy, L.; Engelholm, Lars H.; Behrendt, Niels.

In: Journal of Biological Chemistry, Vol. 286, No. 37, 16.09.2011, p. 32736-32748.

Research output: Contribution to journalArticle

Jürgensen, HJ, Madsen, DH, Ingvarsen, S, Melander, MC, Gårdsvoll, H, Patthy, L, Engelholm, LH & Behrendt, N 2011, 'A novel functional role of collagen glycosylation: Interaction with the endocytic collagen receptor uPARAP/ENDO180', Journal of Biological Chemistry, vol. 286, no. 37, pp. 32736-32748. https://doi.org/10.1074/jbc.M111.266692
Jürgensen, Henrik J. ; Madsen, Daniel H. ; Ingvarsen, Signe ; Melander, Maria C. ; Gårdsvoll, Henrik ; Patthy, L. ; Engelholm, Lars H. ; Behrendt, Niels. / A novel functional role of collagen glycosylation : Interaction with the endocytic collagen receptor uPARAP/ENDO180. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 37. pp. 32736-32748.
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