title: uPARAP/Endo180 is essential for cellular uptake of collagen and promotes fibroblast collagen adhesion.
abstract: 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.
authors.affiliation: Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Lars H
authors.initials: LH
authors.lastname: Engelholm
authors.forename: Karin
authors.initials: K
authors.lastname: List
authors.forename: Sarah
authors.initials: S
authors.lastname: Netzel-Arnett
authors.forename: Edna
authors.initials: E
authors.lastname: Cukierman
authors.forename: David J
authors.initials: DJ
authors.lastname: Mitola
authors.forename: Hannah
authors.initials: H
authors.lastname: Aaronson
authors.forename: Lars
authors.initials: L
authors.lastname: Kjøller
authors.forename: Jørgen K
authors.initials: JK
authors.lastname: Larsen
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Yamada
authors.forename: Dudley K
authors.initials: DK
authors.lastname: Strickland
authors.forename: Kenn
authors.initials: K
authors.lastname: Holmbeck
authors.forename: Keld
authors.initials: K
authors.lastname: Danø
authors.forename: Henning
authors.initials: H
authors.lastname: Birkedal-Hansen
authors.forename: Niels
authors.initials: N
authors.lastname: Behrendt
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Bugge
mesh_terms: 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
chemical_list: 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