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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Adhesion / drug effects
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Cell Movement / drug effects
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Cell Movement / physiology
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Cells, Cultured
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Collagen / metabolism*
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Collagenases / metabolism
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Endocytosis*
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Fibroblasts / metabolism*
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Fibronectins / metabolism
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Gene Deletion
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Matrix Metalloproteinase 13
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Membrane Glycoproteins / chemistry
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism*
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Mice
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Receptors, Cell Surface / chemistry
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Receptors, Cell Surface / deficiency
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / metabolism*
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Receptors, Mitogen / chemistry
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Receptors, Mitogen / deficiency
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Receptors, Mitogen / genetics
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Receptors, Mitogen / metabolism
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Receptors, Urokinase Plasminogen Activator
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Transferrin / metabolism
Substances
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Fibronectins
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Membrane Glycoproteins
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Mrc2 protein, mouse
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Plaur protein, mouse
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Receptors, Cell Surface
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Receptors, Mitogen
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Receptors, Urokinase Plasminogen Activator
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Transferrin
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holotransferrin
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Collagen
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Collagenases
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Matrix Metalloproteinase 13
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Mmp13 protein, mouse