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SCGN deficiency results in colitis susceptibility.
- Source :
-
ELife [Elife] 2019 Oct 30; Vol. 8. Date of Electronic Publication: 2019 Oct 30. - Publication Year :
- 2019
-
Abstract
- Inflammatory bowel disease (IBD) affects 1.5-3.0 million people in the United States. IBD is genetically determined and many common risk alleles have been identified. Yet, a large proportion of genetic predisposition remains unexplained. In this study, we report the identification of an ultr arare missense variant (NM&#95;006998.3:c.230G > A;p.Arg77His) in the SCGN gene causing Mendelian early-onset ulcerative colitis. SCGN encodes a calcium sensor that is exclusively expressed in neuroendocrine lineages, including enteroendocrine cells and gut neurons. SCGN interacts with the SNARE complex, which is required for vesicle fusion with the plasma membrane. We show that the SCGN mutation identified impacted the localization of the SNARE complex partner, SNAP25, leading to impaired hormone release. Finally, we show that mouse models of Scgn deficiency recapitulate impaired hormone release and susceptibility to DSS-induced colitis. Altogether, these studies demonstrate that functional deficiency in SCGN can result in intestinal inflammation and implicates the neuroendocrine cellular compartment in IBD.<br />Competing Interests: LS, HL, EL, ZL, AS, AP, MK, AK, NN, JR, PS, JP, PG, QL, ST, LC, TR, SH, KV, LB, DJ, EB No competing interests declared<br /> (© 2019, Sifuentes-Dominguez et al.)
- Subjects :
- Animals
Cell Membrane metabolism
Cytoplasmic Vesicles metabolism
Disease Models, Animal
Humans
Membrane Fusion
Mice
Mutation, Missense
Protein Transport
SNARE Proteins metabolism
Secretagogins genetics
Synaptosomal-Associated Protein 25 metabolism
Colitis, Ulcerative genetics
Genetic Predisposition to Disease
Secretagogins deficiency
Subjects
Details
- Language :
- English
- ISSN :
- 2050-084X
- Volume :
- 8
- Database :
- MEDLINE
- Journal :
- ELife
- Publication Type :
- Academic Journal
- Accession number :
- 31663849
- Full Text :
- https://doi.org/10.7554/eLife.49910