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Mucus Detachment by Host Metalloprotease Meprin β Requires Shedding of Its Inactive Pro-form, which Is Abrogated by the Pathogenic Protease RgpB.
- Source :
-
Cell reports [Cell Rep] 2017 Nov 21; Vol. 21 (8), pp. 2090-2103. - Publication Year :
- 2017
-
Abstract
- The host metalloprotease meprin β is required for mucin 2 (MUC2) cleavage, which drives intestinal mucus detachment and prevents bacterial overgrowth. To gain access to the cleavage site in MUC2, meprin β must be proteolytically shed from epithelial cells. Hence, regulation of meprin β shedding and activation is important for physiological and pathophysiological conditions. Here, we demonstrate that meprin β activation and shedding are mutually exclusive events. Employing ex vivo small intestinal organoid and cell culture experiments, we found that ADAM-mediated shedding is restricted to the inactive pro-form of meprin β and is completely inhibited upon its conversion to the active form at the cell surface. This strict regulation of meprin β activity can be overridden by pathogens, as demonstrated for the bacterial protease Arg-gingipain (RgpB). This secreted cysteine protease potently converts membrane-bound meprin β into its active form, impairing meprin β shedding and its function as a mucus-detaching protease.<br /> (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Amino Acid Sequence genetics
Animals
Cell Membrane metabolism
Epithelial Cells metabolism
Female
Gingipain Cysteine Endopeptidases
HEK293 Cells
Humans
Male
Metalloendopeptidases genetics
Mice, Transgenic
Mucin-2 genetics
Mucin-2 metabolism
Adhesins, Bacterial metabolism
Cysteine Endopeptidases metabolism
Metalloendopeptidases metabolism
Metalloproteases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 21
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 29166602
- Full Text :
- https://doi.org/10.1016/j.celrep.2017.10.087