The non-phagocytic route of collagen uptake: a distinct degradation pathway

Daniel H Madsen; Signe Ingvarsen; Henrik J Jürgensen; Maria C Melander; Lars Kjøller; Amanda Moyer; Christian Honoré; Maria Charlotte Madsen; Peter Garred; Sven Burgdorf; Thomas H Bugge; Niels Behrendt; Lars H Engelholm

doi:10.1074/jbc.M110.208033

The non-phagocytic route of collagen uptake: a distinct degradation pathway

Daniel H Madsen, Signe Ingvarsen, Henrik J Jürgensen, Maria C Melander, Lars Kjøller, Amanda Moyer, Christian Honoré, Maria Charlotte Madsen, Peter Garred, Sven Burgdorf, Thomas H Bugge, Niels Behrendt, Lars H Engelholm

Department of Clinical Medicine

77 Citations (Scopus)

Abstract

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.

Original language	English
Journal	The Journal of Biological Chemistry
Volume	286
Issue number	30
Pages (from-to)	26996-7010
Number of pages	15
ISSN	0021-9258
DOIs	https://doi.org/10.1074/jbc.M110.208033
Publication status	Published - 29 Jul 2011

Keywords

Animals
Antibodies, Monoclonal, Murine-Derived
Caco-2 Cells
Collagen
Fibroblasts
HEK293 Cells
HeLa Cells
Humans
Lectins, C-Type
Macrophages
Mannose-Binding Lectins
Membrane Glycoproteins
Mice
Mice, Knockout
NIH 3T3 Cells
Phagocytosis
Receptors, Cell Surface

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1074/jbc.M110.208033

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Madsen, D. H., Ingvarsen, S., Jürgensen, H. J., Melander, M. C., Kjøller, L., Moyer, A., Honoré, C., Madsen, M. C., Garred, P., Burgdorf, S., Bugge, T. H., Behrendt, N., & Engelholm, L. H. (2011). The non-phagocytic route of collagen uptake: a distinct degradation pathway. The Journal of Biological Chemistry, 286(30), 26996-7010. https://doi.org/10.1074/jbc.M110.208033

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title = "The non-phagocytic route of collagen uptake: a distinct degradation pathway",

abstract = "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.",

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author = "Madsen, {Daniel H} and Signe Ingvarsen and J{\"u}rgensen, {Henrik J} and Melander, {Maria C} and Lars Kj{\o}ller and Amanda Moyer and Christian Honor{\'e} and Madsen, {Maria Charlotte} and Peter Garred and Sven Burgdorf and Bugge, {Thomas H} and Niels Behrendt and Engelholm, {Lars H}",

year = "2011",

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doi = "10.1074/jbc.M110.208033",

language = "English",

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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

SN - 0021-9258

VL - 286

SP - 26996

EP - 27010

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 30

ER -

The non-phagocytic route of collagen uptake: a distinct degradation pathway

Abstract

Keywords

UN SDGs

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