Integrated Genomics of Crohn’s Disease Risk Variant Identifies a Role for CLEC12A in Antibacterial Autophagy

DSpace/Manakin Repository

Integrated Genomics of Crohn’s Disease Risk Variant Identifies a Role for CLEC12A in Antibacterial Autophagy

Citable link to this page

 

 
Title: Integrated Genomics of Crohn’s Disease Risk Variant Identifies a Role for CLEC12A in Antibacterial Autophagy
Author: Begun, Jakob; Lassen, Kara G.; Jijon, Humberto B.; Baxt, Leigh A.; Goel, Gautam; Heath, Robert J.; Ng, Aylwin; Tam, Jenny M.; Kuo, Szu-Yu; Villablanca, Eduardo J.; Fagbami, Lola; Oosting, Marije; Kumar, Vinod; Schenone, Monica; Carr, Steven A.; Joosten, Leo A.B.; Vyas, Jatin M.; Daly, Mark J.; Netea, Mihai G.; Brown, Gordon D.; Wijmenga, Cisca; Xavier, Ramnik J.

Note: Order does not necessarily reflect citation order of authors.

Citation: Begun, J., K. Lassen, H. Jijon, L. Baxt, G. Goel, R. Heath, A. Ng, et al. 2015. “Integrated Genomics of Crohn’s Disease Risk Variant Identifies a Role for CLEC12A in Antibacterial Autophagy.” Cell Reports 11 (12): 1905-1918. doi:10.1016/j.celrep.2015.05.045. http://dx.doi.org/10.1016/j.celrep.2015.05.045.
Full Text & Related Files:
Abstract: Summary The polymorphism ATG16L1 T300A, associated with increased risk of Crohn’s disease, impairs pathogen defense mechanisms including selective autophagy, but specific pathway interactions altered by the risk allele remain unknown. Here, we use perturbational profiling of human peripheral blood cells to reveal that CLEC12A is regulated in an ATG16L1-T300A-dependent manner. Antibacterial autophagy is impaired in CLEC12A-deficient cells, and this effect is exacerbated in the presence of the ATG16L1∗300A risk allele. Clec12a−/− mice are more susceptible to Salmonella infection, supporting a role for CLEC12A in antibacterial defense pathways in vivo. CLEC12A is recruited to sites of bacterial entry, bacteria-autophagosome complexes, and sites of sterile membrane damage. Integrated genomics identified a functional interaction between CLEC12A and an E3-ubiquitin ligase complex that functions in antibacterial autophagy. These data identify CLEC12A as early adaptor molecule for antibacterial autophagy and highlight perturbational profiling as a method to elucidate defense pathways in complex genetic disease.
Published Version: doi:10.1016/j.celrep.2015.05.045
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4507440/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:21461882
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters