uPARAP/Endo180 is essential for cellular uptake of collagen and promotes fibroblast collagen adhesion.
The uptake and lysosomal degradation of collagen by fibroblasts constitute a major pathway in the turnover of connective tissue. However, the molecular mechanisms governing this pathway are poorly understood. Here, we show that the urokinase plasminogen activator receptor-associated protein (uPARAP)/Endo180, a novel mesenchymally expressed member of the macrophage mannose receptor family of endocytic receptors, is a key player in this process. Fibroblasts from mice with a targeted deletion in the uPARAP/Endo180 gene displayed a near to complete abrogation of collagen endocytosis. Furthermore, these cells had diminished initial adhesion to a range of different collagens, as well as impaired migration on fibrillar collagen. These studies identify a central function of uPARAP/Endo180 in cellular collagen interactions.
Engelholm
Lars H
LH
Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.
List
Karin
K
Netzel-Arnett
Sarah
S
Cukierman
Edna
E
Mitola
David J
DJ
Aaronson
Hannah
H
Kjøller
Lars
L
Larsen
Jørgen K
JK
Yamada
Kenneth M
KM
Strickland
Dudley K
DK
Holmbeck
Kenn
K
Danø
Keld
K
Birkedal-Hansen
Henning
H
Behrendt
Niels
N
Bugge
Thomas H
TH
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D017364:Collagenases / Q000378:metabolism; D004705:Endocytosis; D005347:Fibroblasts / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D017353:Gene Deletion; D053509:Matrix Metalloproteinase 13; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011975:Receptors, Mitogen / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D014168:Transferrin / Q000378:metabolism
D005353:Fibronectins; D008562:Membrane Glycoproteins; C474081:Mrc2 protein, mouse; C524899:Plaur protein, mouse; D011956:Receptors, Cell Surface; D011975:Receptors, Mitogen; D055293:Receptors, Urokinase Plasminogen Activator; D014168:Transferrin; C110714:holotransferrin; D003094:Collagen; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse