Atg16L1 T300A variant decreases selective autophagy resulting in altered cytokine signaling and decreased antibacterial defense

Proceedings of the National Academy of Sciences of the United States of America

Volumn 111, Issue 21, 2014, Pages 7741-7746

  Lassen, Kara G ^a,b   Kuballa, Petric ^a,b   Conway, Kara L ^a,b   Patel, Khushbu K ^c   Becker, Christine E ^b   Peloquin, Joanna M ^b   Villablanca, Eduardo J ^a,b   Norman, Jason M ^c   Liu, Ta Chiang ^c   Heath, Robert J ^a,b   Becker, Morgan L ^c   Fagbami, Lola ^a   Horn, Heiko ^a,b   Mercer, Johnathan ^a   Yilmaz, Omer H ^b,d   Jaffe, Jacob D ^a   Shamji, Alykhan F ^a   Bhan, Atul K ^b   Carr, Steven A ^a   Daly, Mark J ^a,b   Virgin, Herbert W ^c   Schreiber, Stuart L ^a,e   Stappenbeck, Thaddeus S ^c   Xavier, Ramnik J ^a,b   more..

^a BROAD INSTITUTE OF MIT AND HARVARD   (United States)

^b MASSACHUSETTS GENERAL HOSPITAL   (United States)

^c WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^e HARVARD UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE; CASPASE 3; CASPASE 7; CYTOKINE; INTERLEUKIN 1BETA; PROTEIN;

ANIMAL CELL; ANIMAL TISSUE; ANTIBACTERIAL ACTIVITY; ARTICLE; CYTOKINE PRODUCTION; CYTOKINE RELEASE; DENDRITIC CELL; ENTERITIS; GOBLET CELL; HUMAN; HUMAN CELL; MOUSE; NONHUMAN; PANETH CELL; PHENOTYPE; PRIMARY CELL; PRIORITY JOURNAL; PROTEOMICS; SELECTIVE AUTOPHAGY; SMALL INTESTINE; XENOPHAGY;

ANIMALS; AUTOPHAGY; BLOTTING, WESTERN; CARRIER PROTEINS; CHROMATOGRAPHY, LIQUID; CROHN DISEASE; ENZYME-LINKED IMMUNOSORBENT ASSAY; FLOW CYTOMETRY; GENE KNOCK-IN TECHNIQUES; GOBLET CELLS; MICE; PANETH CELLS; POLYMORPHISM, SINGLE NUCLEOTIDE; PROTEOMICS; REAL-TIME POLYMERASE CHAIN REACTION; SALMONELLA INFECTIONS; TANDEM MASS SPECTROMETRY;

EID: 84901660514     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1407001111     Document Type: Article

References (37)

1. Jostins L, et al.; International IBD Genetics Consortium (IIBDGC) (2012) Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491(7422):119-124.
2. Franke A, et al. (2010) Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. Nat Genet 42(12):1118-1125.
3. Rioux JD, et al. (2007) Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat Genet 39(5): 596-604. (Pubitemid 46676115)
4. Khor B, Gardet A, Xavier RJ (2011) Genetics and pathogenesis of inflammatory bowel disease. Nature 474(7351):307-317.
5. Saitoh T, et al. (2008) Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production. Nature 456(7219):264-268.
6. Cadwell K, et al. (2010) Virus-plus-susceptibility gene interaction determines Crohn's disease gene Atg16L1 phenotypes in intestine. Cell 141(7):1135-1145.
7. Cadwell K, et al. (2008) A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells. Nature 456(7219):259-263.
8. Adolph TE, et al. (2013) Paneth cells as a site of origin for intestinal inflammation. Nature 503(7475):272-276.
9. Conway KL, et al. (2013) Atg16l1 is required for autophagy in intestinal epithelial cells and protection of mice from Salmonella infection. Gastroenterology 145(6): 1347-1357.
10. Patel KK, et al. (2013) Autophagy proteins control goblet cell function by potentiating reactive oxygen species production. EMBO J 32(24):3130-3144.
11. Plantinga TS, et al. (2011) Crohn's disease-associated ATG16L1 polymorphism modulates pro-inflammatory cytokine responses selectively upon activation of NOD2. Gut 60(9):1229-1235.
12. Kuballa P, Huett A, Rioux JD, Daly MJ, Xavier RJ (2008) Impaired autophagy of an intracellular pathogen induced by a Crohn's disease associated ATG16L1 variant. PLoS ONE 3(10):e3391.
13. Travassos LH, et al. (2010) Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry. Nat Immunol 11(1):55-62.
14. Cooney R, et al. (2010) NOD2 stimulation induces autophagy in dendritic cells influencing bacterial handling and antigen presentation. Nat Med 16(1):90-97.
15. Fujita N, et al. (2009) Differential involvement of Atg16L1 in Crohn disease and canonical autophagy: Analysis of the organization of the Atg16L1 complex in fibro-blasts. J Biol Chem 284(47):32602-32609.
16. Zheng H, et al. (2004) Cloning and analysis of human Apg16L. DNA Seq 15(4):303-305. (Pubitemid 39440425)
17. VanDussen KL, et al. (2014) Genetic variants synthesize to produce Paneth cell phe-notypes that define subtypes of Crohn's disease. Gastroenterology 146(1):200-209.
18. Sato T, et al. (2011) Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature 469(7330):415-418.
19. Korn LL, et al. (2014) Conventional CD4+ T cells regulate IL-22-producing intestinal innate lymphoid cells. Mucosal Immunol, 10.1038/mi.2013.121.
20. Kim TH, Escudero S, Shivdasani RA (2012) Intact function of Lgr5 receptor-expressing intestinal stem cells in the absence of Paneth cells. Proc Natl Acad Sci USA 109(10): 3932-3937.
21. Mahrus S, et al. (2008) Global sequencing of proteolytic cleavage sites in apoptosis by specific labeling of protein N termini. Cell 134(5):866-876.
22. Ogawa M, et al. (2005) Escape of intracellular Shigella from autophagy. Science 307(5710):727-731. (Pubitemid 40194643)
23. Behrends C, Sowa ME, Gygi SP, Harper JW (2010) Network organization of the human autophagy system. Nature 466(7302):68-76.
24. Itoh T, et al. (2008) Golgi-resident small GTPase Rab33B interacts with Atg16L and modulates autophagosome formation. Mol Biol Cell 19(7):2916-2925.
25. Miraoui H, et al. (2013) Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism. Am J Hum Genet 92(5):725-743.
26. Thurston TL, Wandel MP, von Muhlinen N, Foeglein A, Randow F (2012) Galectin 8 targets damaged vesicles for autophagy to defend cells against bacterial invasion. Nature 482(7385):414-418.
27. Orvedahl A, et al. (2011) Image-based genome-wide siRNA screen identifies selective autophagy factors. Nature 480(7375):113-117.
28. Murthy A, et al. (2014) A Crohn's disease variant in Atg16l1 enhances its degradation by caspase 3. Nature 506(7489):456-462.
29. Wlodarska M, et al. (2014) NLRP6 inflammasome orchestrates the colonic host-microbial interface by regulating goblet cell mucus secretion. Cell 156(5):1045-1059.
30. Patel KK, Stappenbeck TS (2013) Autophagy and intestinal homeostasis. Annu Rev Physiol 75:241-262.
31. Becker C, Watson AJ, Neurath MF (2013) Complex roles of caspases in the patho-genesis of inflammatory bowel disease. Gastroenterology 144(2):283-293.
32. Jonsson T, et al. (2012) A mutation in APP protects against Alzheimer's disease and age-related cognitive decline. Nature 488(7409):96-99.
33. Warner N, et al. (2013) A genome-wide siRNA screen reveals positive and negative regulators of the NOD2 and NF-κB signaling pathways. Sci Signal 6(258):rs3.
34. Harris J, et al. (2011) Autophagy controls IL-1beta secretion by targeting pro-IL-1beta for degradation. J Biol Chem 286(11):9587-9597.
35. Shaw SY, et al. (2013) Selective modulation of autophagy, innate immunity, and adaptive immunity by small molecules. ACS Chem Biol 8(12):2724-2733.
36. Huett A, et al. (2009) A novel hybrid yeast-human network analysis reveals an essential role for FNBP1L in antibacterial autophagy. J Immunol 182(8):4917-4930.
37. Huett A, et al. (2012) The LRR and RING domain protein LRSAM1 is an E3 ligase crucial for ubiquitin-dependent autophagy of intracellular Salmonella Typhimurium. Cell Host Microbe 12(6):778-790.