期刊
DEVELOPMENT
卷 144, 期 21, 页码 3990-4001出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.147033
关键词
Atg16; Drosophila; Inflammation; Intestine; Rab19; Slit
资金
- Hungarian Academy of Sciences (Magyar Tudomanyos Akademia) [Momentum LP-2014/2]
- National Research, Development and Innovation Office (Nemzeti Kutatasi, Fejlesztesi es Innovacios Hivatal) [PD115568, PD112632, K119842, GINOP-2.3.2-15-2016-00032]
Genetic variations of Atg16l1, Slit2 and Rab19 predispose to the development of inflammatory bowel disease (IBD), but the relationship between these mutations is unclear. Here we show that in Drosophila guts lacking the WD40 domain of Atg16, pre-enteroendocrine (pre-EE) cells accumulate that fail to differentiate into properly functioning secretory EE cells. Mechanistically, loss of Atg16 or its binding partner Rab19 impairs Slit production, which normally inhibits EE cell generation by activating Robo signaling in stem cells. Importantly, loss of Atg16 or decreased Slit/Robo signaling triggers an intestinal inflammatory response. Surprisingly, analysis of Rab19 and domain-specific Atg16 mutants indicates that their stem cell niche regulatory function is independent of autophagy. Our study reveals how mutations in these different genes may contribute to IBD.
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