A novel functional role of collagen glycosylation: interaction with the endocytic collagen receptor uPARAP/ENDO 180

TY - JOUR

T1 - A novel functional role of collagen glycosylation

T2 - interaction with the endocytic collagen receptor uPARAP/ENDO 180

AU - Jürgensen, Henrik J

AU - Madsen, Daniel H

AU - Ingvarsen, Signe

AU - Melander, Maria C

AU - Gårdsvoll, Henrik

AU - Patthy, Laszlo

AU - Engelholm, Lars H

AU - Behrendt, Niels

PY - 2011/9/16

Y1 - 2011/9/16

N2 - 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.

AB - 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.

KW - Animals

KW - Cell Line, Tumor

KW - Collagen Type IV

KW - Extracellular Matrix

KW - Glycosylation

KW - Humans

KW - Lectins, C-Type

KW - Mannose-Binding Lectins

KW - Membrane Glycoproteins

KW - Mice

KW - Mice, Mutant Strains

KW - Protein Structure, Tertiary

KW - Receptors, Cell Surface

KW - Recombinant Proteins

U2 - 10.1074/jbc.M111.266692

DO - 10.1074/jbc.M111.266692

M3 - Journal article

C2 - 21768090

SN - 0021-9258

VL - 286

SP - 32736

EP - 32748

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 37

ER -