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- Title
Trans-Golgi protein TVP23B regulates host-microbe interactions via Paneth cell homeostasis and Goblet cell glycosylation.
- Authors
Song, Ran; McAlpine, William; Fond, Aaron M.; Nair-Gill, Evan; Choi, Jin Huk; Nyström, Elisabeth E. L.; Arike, Liisa; Field, Sydney; Li, Xiaohong; SoRelle, Jeffrey A.; Moresco, James J.; Moresco, Eva Marie Y.; Yates 3rd, John R.; Azadi, Parastoo; Ni, Josephine; Birchenough, George M. H.; Beutler, Bruce; Turer, Emre E.
- Abstract
A key feature in intestinal immunity is the dynamic intestinal barrier, which separates the host from resident and pathogenic microbiota through a mucus gel impregnated with antimicrobial peptides. Using a forward genetic screen, we have found a mutation in Tvp23b, which conferred susceptibility to chemically induced and infectious colitis. Trans-Golgi apparatus membrane protein TVP23 homolog B (TVP23B) is a transmembrane protein conserved from yeast to humans. We found that TVP23B controls the homeostasis of Paneth cells and function of goblet cells, leading to a decrease in antimicrobial peptides and more penetrable mucus layer. TVP23B binds with another Golgi protein, YIPF6, which is similarly critical for intestinal homeostasis. The Golgi proteomes of YIPF6 and TVP23B-deficient colonocytes have a common deficiency of several critical glycosylation enzymes. TVP23B is necessary for the formation of the sterile mucin layer of the intestine and its absence disturbs the balance of host and microbe in vivo. Increased susceptibility to gastrointestinal infections and colitis can be driven by a failure to maintain intestinal homeostasis. Here, using a forward genetic screen, Song et al. identify and characterise the role of TVP23B in Paneth cell and goblet cell function, and its impact on colitis.
- Subjects
GOLGI apparatus; MEMBRANE proteins; GLYCOSYLATION; ANTIMICROBIAL peptides; HOMEOSTASIS; CELL physiology; GENETIC testing
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-39398-1