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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 Reports, Vol 21, Iss 8, Pp 2090-2103 (2017)
- Publication Year :
- 2017
-
Abstract
- Summary 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.
- Subjects :
- 0301 basic medicine
Male
metalloprotease
medicine.medical_treatment
Cell
Mice, Transgenic
Mucin 2
Biology
General Biochemistry, Genetics and Molecular Biology
Microbiology
03 medical and health sciences
mucus
Organoid
medicine
intestinal mucus barrier
Animals
Humans
Amino Acid Sequence
Adhesins, Bacterial
lcsh:QH301-705.5
Metalloproteinase
Mucin-2
host-microbiome interaction
Protease
030102 biochemistry & molecular biology
Protein
Cell Membrane
Metalloendopeptidases
Epithelial Cells
Mucus
Cysteine protease
Cell biology
Cysteine Endopeptidases
030104 developmental biology
medicine.anatomical_structure
HEK293 Cells
lcsh:Biology (General)
Cell culture
Gingipain Cysteine Endopeptidases
Metalloproteases
Female
ectodomain shedding
Schleim
Subjects
Details
- ISSN :
- 22111247
- Database :
- OpenAIRE
- Journal :
- CELL Reports
- Accession number :
- edsair.doi.dedup.....943335444ab81a7ba427f9d90932dcf3
- Full Text :
- https://doi.org/10.1016/j.celrep.2017.10.087