The Non-phagocytic Route of Collagen Uptake
Murine-Derived
0301 basic medicine
Knockout
Receptors, Cell Surface
Antibodies
Antibodies, Monoclonal, Murine-Derived
Mice
03 medical and health sciences
Phagocytosis
Lectins
Monoclonal
Receptors
Animals
Humans
Lectins, C-Type
Mice, Knockout
Membrane Glycoproteins
C-Type
Macrophages
Fibroblasts
HEK293 Cells
Mannose-Binding Lectins
Cell Surface
NIH 3T3 Cells
Collagen
Caco-2 Cells
Mannose Receptor
HeLa Cells
DOI:
10.1074/jbc.m110.208033
Publication Date:
2011-06-08T04:18:09Z
AUTHORS (13)
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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