Proteolytic processing of galectin-3 by meprin metalloproteases is crucial for host-microbiome homeostasis
Abstract: The metalloproteases meprin α and meprin β are highly expressed in the healthy gut but significantly decreased in inflammatory bowel disease, implicating a protective role in mucosal homeostasis. In the colon, meprin α and meprin β form covalently linked heterodimers tethering meprin α to the plasma membrane, therefore presenting dual proteolytic activity in a unique enzyme complex. To unravel its function, we applied N-terminomics and identified galectin-3 as the major intestinal substrate for meprin α/β heterodimers. Galectin-3–deficient and meprin α/β double knockout mice show similar alterations in their microbiome in comparison to wild-type mice. We further demonstrate that meprin α/β heterodimers differentially process galectin-3 upon bacterial infection, in germ-free, conventionally housed (specific pathogen–free), or wildling mice, which in turn regulates the bacterial agglutination properties of galectin-3. Thus, the constitutive cleavage of galectin-3 by meprin α/β heterodimers may play a key role in colon host-microbiome homeostasis
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Anmerkungen
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Science advances. - 9, 13 (2023) , adf4055, ISSN: 2375-2548
- Ereignis
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Veröffentlichung
- (wo)
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Freiburg
- (wer)
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Universität
- (wann)
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2023
- Urheber
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Bülck, Cynthia
Nyström, Elisabeth E. L.
Koudelka, Tomas
Mannbar-Frahm, Michael
Andresen, Gerrit
Radhouani, Mariem
Tran, Florian
Scharfenberg, Franka
Schrell, Friederike
Armbrust, Fred
Dahlke, Eileen
Zhao, Bei
Vervaeke, Alex
Theilig, Franziska
Rosenstiel, Philip
Starkl, Philipp
Roßhart, Stephan Patrick
Fickenscher, Helmut
Tholey, Andreas
Hansson, Gunnar C.
Becker-Pauly, Christoph
- DOI
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10.1126/sciadv.adf4055
- URN
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urn:nbn:de:bsz:25-freidok-2352647
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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25.03.2025, 13:48 MEZ
Datenpartner
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- Bülck, Cynthia
- Nyström, Elisabeth E. L.
- Koudelka, Tomas
- Mannbar-Frahm, Michael
- Andresen, Gerrit
- Radhouani, Mariem
- Tran, Florian
- Scharfenberg, Franka
- Schrell, Friederike
- Armbrust, Fred
- Dahlke, Eileen
- Zhao, Bei
- Vervaeke, Alex
- Theilig, Franziska
- Rosenstiel, Philip
- Starkl, Philipp
- Roßhart, Stephan Patrick
- Fickenscher, Helmut
- Tholey, Andreas
- Hansson, Gunnar C.
- Becker-Pauly, Christoph
- Universität
Entstanden
- 2023
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