| Autor: |
Cynthia Bülck, Elisabeth E. L. Nyström, Tomas Koudelka, Michael Mannbar-Frahm, Gerrit Andresen, Mariem Radhouani, Florian Tran, Franka Scharfenberg, Friederike Schrell, Fred Armbrust, Eileen Dahlke, Bei Zhao, Alex Vervaeke, Franziska Theilig, Philip Rosenstiel, Philipp Starkl, Stephan P. Rosshart, Helmut Fickenscher, Andreas Tholey, Gunnar C. Hansson, Christoph Becker-Pauly |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
Science Advances. 9 |
| ISSN: |
2375-2548 |
| DOI: |
10.1126/sciadv.adf4055 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
