The non-phagocytic route of collagen uptake: a distinct degradation pathway
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The non-phagocytic route of collagen uptake : a distinct degradation pathway. / Madsen, Daniel H; Ingvarsen, Signe; Jürgensen, Henrik J; Melander, Maria C; Kjøller, Lars; Moyer, Amanda; Honoré, Christian; Madsen, Maria Charlotte; Garred, Peter; Burgdorf, Sven; Bugge, Thomas H; Behrendt, Niels; Engelholm, Lars H.
I: The Journal of Biological Chemistry, Bind 286, Nr. 30, 29.07.2011, s. 26996-7010.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - The non-phagocytic route of collagen uptake
T2 - a distinct degradation pathway
AU - Madsen, Daniel H
AU - Ingvarsen, Signe
AU - Jürgensen, Henrik J
AU - Melander, Maria C
AU - Kjøller, Lars
AU - Moyer, Amanda
AU - Honoré, Christian
AU - Madsen, Maria Charlotte
AU - Garred, Peter
AU - Burgdorf, Sven
AU - Bugge, Thomas H
AU - Behrendt, Niels
AU - Engelholm, Lars H
PY - 2011/7/29
Y1 - 2011/7/29
N2 - The degradation of collagens, the most abundant proteins of the extracellular matrix, is involved in numerous physiological and pathological conditions including cancer invasion. An important turnover pathway involves cellular internalization and degradation of large, soluble collagen fragments, generated by initial cleavage of the insoluble collagen fibers. We have previously observed that in primary mouse fibroblasts, this endocytosis of collagen fragments is dependent on the receptor urokinase plasminogen activator receptor-associated protein (uPARAP)/Endo180. Others have identified additional mechanisms of collagen uptake, with different associated receptors, in other cell types. These receptors include β1-integrins, being responsible for collagen phagocytosis, and the mannose receptor. We have now utilized a newly developed monoclonal antibody against uPARAP/Endo180, which down-regulates the receptor protein level on treated cells, to examine the role of uPARAP/Endo180 as a mediator of collagen internalization by a wide range of cultured cell types. With the exception of macrophages, all cells that proved capable of efficient collagen internalization were of mesenchymal origin and all of these utilized uPARAP/Endo180 for their collagen uptake process. Macrophages internalized collagen in a process mediated by the mannose receptor, a protein belonging to the same protein family as uPARAP/Endo180. β1-Integrins were found not to be involved in the endocytosis of soluble collagen, irrespectively of whether this was mediated by uPARAP/Endo180 or the mannose receptor. This further distinguishes these pathways from the phagocytic uptake of particulate collagen.
AB - The degradation of collagens, the most abundant proteins of the extracellular matrix, is involved in numerous physiological and pathological conditions including cancer invasion. An important turnover pathway involves cellular internalization and degradation of large, soluble collagen fragments, generated by initial cleavage of the insoluble collagen fibers. We have previously observed that in primary mouse fibroblasts, this endocytosis of collagen fragments is dependent on the receptor urokinase plasminogen activator receptor-associated protein (uPARAP)/Endo180. Others have identified additional mechanisms of collagen uptake, with different associated receptors, in other cell types. These receptors include β1-integrins, being responsible for collagen phagocytosis, and the mannose receptor. We have now utilized a newly developed monoclonal antibody against uPARAP/Endo180, which down-regulates the receptor protein level on treated cells, to examine the role of uPARAP/Endo180 as a mediator of collagen internalization by a wide range of cultured cell types. With the exception of macrophages, all cells that proved capable of efficient collagen internalization were of mesenchymal origin and all of these utilized uPARAP/Endo180 for their collagen uptake process. Macrophages internalized collagen in a process mediated by the mannose receptor, a protein belonging to the same protein family as uPARAP/Endo180. β1-Integrins were found not to be involved in the endocytosis of soluble collagen, irrespectively of whether this was mediated by uPARAP/Endo180 or the mannose receptor. This further distinguishes these pathways from the phagocytic uptake of particulate collagen.
KW - Animals
KW - Antibodies, Monoclonal, Murine-Derived
KW - Caco-2 Cells
KW - Collagen
KW - Fibroblasts
KW - HEK293 Cells
KW - HeLa Cells
KW - Humans
KW - Lectins, C-Type
KW - Macrophages
KW - Mannose-Binding Lectins
KW - Membrane Glycoproteins
KW - Mice
KW - Mice, Knockout
KW - NIH 3T3 Cells
KW - Phagocytosis
KW - Receptors, Cell Surface
U2 - 10.1074/jbc.M110.208033
DO - 10.1074/jbc.M110.208033
M3 - Journal article
C2 - 21652704
VL - 286
SP - 26996
EP - 27010
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 30
ER -
ID: 107123221