Proteolytic processing of galectin-3 by meprin metalloproteases is crucial for host-microbiome homeostasis

Bülck C, Nyström EE, Koudelka T, Mannbar-Frahm M, Andresen G, Radhouani M, Tran F, Scharfenberg F, Schrell F, Armbrust F, Dahlke E, Zhao B, Vervaeke A, Theilig F, Rosenstiel P, Starkl P, Rosshart SP, Fickenscher H, Tholey A, Hansson GC, Becker-Pauly C (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Science Advances American Association for the Advancement of Science

Book Volume: 9

Pages Range: eadf4055-

Journal Issue: 13

DOI: 10.1126/sciadv.adf4055

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.

Authors with CRIS profile

Stephan Patrick Rosshart Professur für Mikrobiomik

Involved external institutions

Christian-Albrechts-Universität zu Kiel DE Germany (DE) Medizinische Universität Wien AT Austria (AT) University of Gothenburg / Göteborgs universitet SE Sweden (SE)

How to cite

APA:

Bülck, C., Nyström, E.E., Koudelka, T., Mannbar-Frahm, M., Andresen, G., Radhouani, M.,... Becker-Pauly, C. (2023). Proteolytic processing of galectin-3 by meprin metalloproteases is crucial for host-microbiome homeostasis. Science Advances, 9(13), eadf4055-. https://dx.doi.org/10.1126/sciadv.adf4055

MLA:

Bülck, Cynthia, et al. "Proteolytic processing of galectin-3 by meprin metalloproteases is crucial for host-microbiome homeostasis." Science Advances 9.13 (2023): eadf4055-.

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