| First Author | Wichert R | Year | 2017 |
| Journal | Cell Rep | Volume | 21 |
| Issue | 8 | Pages | 2090-2103 |
| PubMed ID | 29166602 | Mgi Jnum | J:254707 |
| Mgi Id | MGI:6103924 | Doi | 10.1016/j.celrep.2017.10.087 |
| Citation | Wichert R, et al. (2017) Mucus Detachment by Host Metalloprotease Meprin beta Requires Shedding of Its Inactive Pro-form, which Is Abrogated by the Pathogenic Protease RgpB. Cell Rep 21(8):2090-2103 |
| abstractText | The host metalloprotease meprin beta 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 beta must be proteolytically shed from epithelial cells. Hence, regulation of meprin beta shedding and activation is important for physiological and pathophysiological conditions. Here, we demonstrate that meprin beta 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 beta and is completely inhibited upon its conversion to the active form at the cell surface. This strict regulation of meprin beta activity can be overridden by pathogens, as demonstrated for the bacterial protease Arg-gingipain (RgpB). This secreted cysteine protease potently converts membrane-bound meprin beta into its active form, impairing meprin beta shedding and its function as a mucus-detaching protease. |
