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

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch
Notes
Science advances. - 9, 13 (2023) , adf4055, ISSN: 2375-2548

Event
Veröffentlichung
(where)
Freiburg
(who)
Universität
(when)
2023
Creator
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
10.1126/sciadv.adf4055
URN
urn:nbn:de:bsz:25-freidok-2352647
Rights
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Last update
25.03.2025, 1:48 PM CET

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Associated

Time of origin

  • 2023

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