eLife, 2019-10, Vol.8
- Sifuentes-Dominguez, Luis F
- Li, Haiying
- Llano, Ernesto
- Liu, Zhe
- Singla, Amika
- Patel, Ashish S
- Kathania, Mahesh
- Khoury, Areen
- Norris, Nicholas
- Rios, Jonathan J
- Starokadomskyy, Petro
- Park, Jason Y
- Gopal, Purva
- Liu, Qi
- Tan, Shuai
- Chan, Lillienne
- Ross, Theodora
- Harrison, Steven
- Venuprasad, K
- Baker, Linda A
- Jia, Da
- Burstein, Ezra
2019
Details
- Autor(en) / Beteiligte
- Sifuentes-Dominguez, Luis F
- Li, Haiying
- Llano, Ernesto
- Liu, Zhe
- Singla, Amika
- Patel, Ashish S
- Kathania, Mahesh
- Khoury, Areen
- Norris, Nicholas
- Rios, Jonathan J
- Starokadomskyy, Petro
- Park, Jason Y
- Gopal, Purva
- Liu, Qi
- Tan, Shuai
- Chan, Lillienne
- Ross, Theodora
- Harrison, Steven
- Venuprasad, K
- Baker, Linda A
- Jia, Da
- Burstein, Ezra
- Titel
- SCGN deficiency results in colitis susceptibility
- Ist Teil von
- eLife, 2019-10, Vol.8
- Ort / Verlag
- England: eLife Sciences Publications Ltd
- Erscheinungsjahr
- 2019
- Link zum Volltext
- Quelle
- EZB Free E-Journals
- Beschreibungen/Notizen
- 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_006998.3:c.230G > A;p.Arg77His) in the gene causing Mendelian early-onset ulcerative colitis. 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 mutation identified impacted the localization of the SNARE complex partner, SNAP25, leading to impaired hormone release. Finally, we show that mouse models of 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2050-084XeISSN: 2050-084XDOI: 10.7554/eLife.49910Titel-ID: cdi_doaj_primary_oai_doaj_org_article_dd63f37bb27b42538ad9d4b24982c8fb
- Format
- –
- Schlagworte
- Age, Animal models, Animals, Calcium, Cell Membrane - metabolism, Colitis, Ulcerative - genetics, Cytoplasmic Vesicles - metabolism, Disease, Disease Models, Animal, Endoscopy, Gene expression, genetic diseases, Genetic Predisposition to Disease, Genetics and Genomics, Genotype & phenotype, Homeostasis, Hormone release, Humans, Immunology and Inflammation, Inflammatory bowel disease, Inflammatory bowel diseases, Intestine, Laboratories, Localization, Membrane Fusion, Mice, Motility, Mutation, Mutation, Missense, neuroendocrine cells, Pathogenesis, Protein Transport, Proteins, scgn, Secretagogins - deficiency, Secretagogins - genetics, Siblings, SNAP receptors, SNAP-25 protein, snare, SNARE Proteins - metabolism, Statistical analysis, Synaptosomal-Associated Protein 25 - metabolism, Ulcerative colitis, Vesicle fusion