Protein Turnover in Epithelial Cells and Mucus along the Gastrointestinal Tract Is Coordinated by the Spatial Location and Microbiota

• Published in: Cell reports (Cambridge) 2020-01, Vol.30 (4), p.1077-1087.e3
• Main Authors: Arike, Liisa, Seiman, Andrus, van der Post, Sjoerd, Rodriguez Piñeiro, Ana M., Ermund, Anna, Schütte, André, Bäckhed, Fredrik, Johansson, Malin E.V., Hansson, Gunnar C.
• Format: Article
• Language: English
• Subjects: amino-acid-metabolism; Animals; bacteria; Cell Biology; chain fatty-acids; Clinical Medicine; colon; colonization; commensals; crypt; diet; dynamics; Epithelial Cells - metabolism; expression; Gastrointestinal Tract - physiology; germ-free; gut microbiota; Humans; kinetics; Klinisk medicin; mass spectrometry; Mice; Microbiota - physiology; Mucus - cytology; Mucus - metabolism; Protein Transport - physiology; protein turnover; proteomics; Proteomics - methods; small intestine; transport
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2019.12.068

The gastrointestinal tract is covered by a single layer of epithelial cells that, together with the mucus layers, protect the underlying tissue from microbial invasion. The epithelium has one of the highest turnover rates in the body. Using stable isotope labeling, high-resolution mass spectrometry, and computational analysis, we report a comprehensive dataset of the turnover of more than 3,000 and the expression of more than 5,000 intestinal epithelial cell proteins, analyzed under conventional and germ-free conditions across five different segments in mouse intestine. The median protein half-life is shorter in the small intestine than in the colon. Differences in protein turnover rates along the intestinal tract can be explained by distinct physiological and immune-related functions between the small and large intestine. An absence of microbiota results in an approximately 1 day longer protein half-life in germ-free animals. [Display omitted] •Dataset of protein turnover rate and expression along the mice intestinal tract•Protein turnover rate is slower in colon than in small intestine•Median protein half-life is 1 day longer in germ-free mice Arike et al. report a turnover rate of >3,000 and expression of >5,000 proteins in epithelial cells and mucus along the mice gastrointestinal tract. Protein turnover rate is faster in the small intestine than in the colon and slower in germ-free animals.