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Impaired Autophagy of an Intracellular Pathogen Induced by a Crohn’s Disease Associated ATG16L1 Variant (2008)
| Citations: | 10 - 0 self |
BibTeX
@MISC{Kuballa08impairedautophagy,
author = {Petric Kuballa and Alan Huett and John D. Rioux and Mark J. Daly and Ramnik J. Xavier},
title = {Impaired Autophagy of an Intracellular Pathogen Induced by a Crohn’s Disease Associated ATG16L1 Variant},
year = {2008}
}
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Abstract
The genetic risk factors predisposing individuals to the development of inflammatory bowel disease are beginning to be deciphered by genome-wide association studies. Surprisingly, these new data point towards a critical role of autophagy in the pathogenesis of Crohn’s disease. A single common coding variant in the autophagy protein ATG16L1 predisposes individuals to the development of Crohn’s disease: while ATG16L1 encoding threonine at amino acid position 300 (ATG16L1*300T) confers protection, ATG16L1 encoding for alanine instead of threonine (ATG16L1*300A, also known as T300A) mediates risk towards the development of Crohn’s disease. Here we report that, in human epithelial cells, the Crohn’s disease-associated ATG16L1 coding variant shows impairment in the capture of internalized Salmonella within autophagosomes. Thus, we propose that the association of ATG16L1*300A with increased risk of Crohn’s disease is due to impaired bacterial handling and lowered rates of bacterial capture by autophagy.
Keyphrases
crohn disease impaired autophagy crohn disease associated atg16l1 variant intracellular pathogen induced autophagy protein atg16l1 confers protection genetic risk factor new data point bacterial capture impaired bacterial handling internalized salmonella genome-wide association study critical role amino acid position human epithelial cell inflammatory bowel disease disease-associated atg16l1 coding variant
