Wichert, RielanaRielanaWichertErmund, AnnaAnnaErmundSchmidt, StefanieStefanieSchmidtSchweinlin, MatthiasMatthiasSchweinlinKsiazek, MiroslawMiroslawKsiazekArnold, PhilippPhilippArnoldKnittler, KatharinaKatharinaKnittlerWilkens, FrederikeFrederikeWilkensPotempa, BarbaraBarbaraPotempaRabe, BjörnBjörnRabeStirnberg, MaritMaritStirnbergLucius, RalphRalphLuciusBartsch, Jörg W.Jörg W.BartschNikolaus, SusannaSusannaNikolausFalk-Paulsen, MarenMarenFalk-PaulsenRosenstiel, PhilipPhilipRosenstielMetzger, MarcoMarcoMetzgerRose-John, StefanStefanRose-JohnPotempa, JanJanPotempaHansson, Gunnar C.Gunnar C.HanssonDempsey, Peter J.Peter J.DempseyBecker-Pauly, ChristophChristophBecker-Pauly2022-03-052022-03-052017https://publica.fraunhofer.de/handle/publica/25125610.1016/j.celrep.2017.10.087The host metalloprotease meprin v 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 v must be proteolytically shed from epithelial cells. Hence, regulation of meprin v shedding and activation is important for physiological and pathophysiological conditions. Here, we demonstrate that meprin v 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 v and is completely inhibited upon its conversion to the active form at the cell surface. This strict regulation of meprin v activity can be overridden by pathogens, as demonstrated for the bacterial protease Arg-gingipain (RgpB). This secreted cysteine protease potently converts membrane-bound meprin v into its active form, impairing meprin v shedding and its function as a mucus-detaching protease.enSchleimProtein660666610620journal article