Frizzled proteins are colonic epithelial receptors for C. difficile toxin B

Nature

Volumn 538, Issue 7625, 2016, Pages 350-355

  Tao, Liang ^a,b   Zhang, Jie ^a,b   Meraner, Paul ^c   Tovaglieri, Alessio ^a   Wu, Xiaoqian ^d   Gerhard, Ralf ^e   Zhang, Xinjun ^a,b   Stallcup, William B ^f   Miao, Ji ^a,b   He, Xi ^a,b   Hurdle, Julian G ^d   Breault, David T ^a,b,g   Brass, Abraham L ^c,h   Dong, Min ^a,b  

^a BOSTON CHILDREN S HOSPITAL   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

^c UNIVERSITY OF MASSACHUSETTS   (United States)

^d TEXAS A AND M HEALTH SCIENCE CENTER   (United States)

^e HANNOVER MEDICAL SCHOOL   (Germany)

^f BURNHAM INSTITUTE   (United States)

^g HARVARD STEM CELL INSTITUTE   (United States)

^h UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CLOSTRIDIUM DIFFICILE TOXIN B; CYSTEINE; FRIZZLED PROTEIN; FRIZZLED PROTEIN 1; FRIZZLED PROTEIN 2; FRIZZLED PROTEIN 7; RECEPTOR; TCDB RECEPTOR; UNCLASSIFIED DRUG; ANTIGEN; BACTERIAL PROTEIN; BACTERIAL TOXIN; CHONDROITIN SULFATE PROTEOGLYCAN 4; OLIGOPEPTIDE; PROTEOGLYCAN; TOXB PROTEIN, CLOSTRIDIUM DIFFICILE; VIRULENCE FACTOR; WNT PROTEIN;

CELLS AND CELL COMPONENTS; DISEASE INCIDENCE; PHYSIOLOGY; PROTEIN; RODENT; TOXIN; VIRULENCE;

ANIMAL EXPERIMENT; ARTICLE; BINDING AFFINITY; BINDING SITE; COLON MUCOSA; CONTROLLED STUDY; CRISPR CAS SYSTEM; HUMAN; HUMAN CELL; IN VIVO STUDY; MOUSE; NONHUMAN; PRIORITY JOURNAL; RECEPTOR BINDING; TISSUE INJURY; ANIMAL; CELL LINE; CHEMISTRY; CHO CELL LINE; COLON; CRICETULUS; CYTOPLASM; DEFICIENCY; EPITHELIUM; FEMALE; GENE INACTIVATION; GENETICS; KNOCKOUT MOUSE; MALE; METABOLISM; PATHOGENICITY; PEPTOCLOSTRIDIUM DIFFICILE; PROTEIN DOMAIN;

CLOSTRIDIUM DIFFICILE; MUS;

ANIMALS; ANTIGENS; BACTERIAL PROTEINS; BACTERIAL TOXINS; BINDING SITES; CELL LINE; CHO CELLS; CLOSTRIDIUM DIFFICILE; COLON; CRICETULUS; CRISPR-CAS SYSTEMS; EPITHELIUM; FEMALE; FRIZZLED RECEPTORS; GENE KNOCKOUT TECHNIQUES; HUMANS; MALE; MICE; MICE, KNOCKOUT; OLIGOPEPTIDES; ORGANOIDS; PROTEIN DOMAINS; PROTEOGLYCANS; VIRULENCE FACTORS; WNT PROTEINS;

EID: 84992391514     PISSN: 00280836     EISSN: 14764687     Source Type: Journal    
DOI: 10.1038/nature19799     Document Type: Article

References (54)

1. Lyerly, D. M., Krivan, H. C., Wilkins, T. D. Clostridium difficile: its disease and toxins. Clin. Microbiol. Rev. 1, 1-18 (1988).
2. Rupnik, M., Wilcox, M. H., Gerding, D. N. Clostridium difficile infection: new developments in epidemiology and pathogenesis. Nature Rev. Microbiol. 7, 526-536 (2009).
3. Heinlen, L., Ballard, J. D. Clostridium difficile infection. Am. J. Med. Sci. 340, 247-252 (2010).
4. Voth, D. E., Ballard, J. D. Clostridium difficile toxins: mechanism of action and role in disease. Clin. Microbiol. Rev. 18, 247-263 (2005).
5. Hunt, J. J., Ballard, J. D. Variations in virulence and molecular biology among emerging strains of Clostridium difficile. Microbiol. Mol. Biol. Rev. 77, 567-581 (2013).
6. Lessa, F. C. et al. Burden of Clostridium difficile infection in the United States. N. Engl. J. Med. 372, 825-834 (2015).
7. Jank, T., Aktories, K. Structure and mode of action of clostridial glucosylating toxins: the ABCD model. Trends Microbiol. 16, 222-229 (2008).
8. Sun, X., Savidge, T., Feng, H. The enterotoxicity of Clostridium difficile toxins. Toxins (Basel) 2, 1848-1880 (2010).
9. Pruitt, R. N., Lacy, D. B. Toward a structural understanding of Clostridium difficile toxins A and B. Front. Cell. Infect. Microbiol. 2, 28 (2012).
10. Just, I. et al. Glucosylation of Rho proteins by Clostridium difficile toxin B. Nature 375, 500-503 (1995).
11. Drudy, D., Fanning, S., Kyne, L. Toxin A-negative, toxin B-positive Clostridium difficile. Int. J. Infect. Dis. 11, 5-10 (2007).
12. Lyras, D. et al. Toxin B is essential for virulence of Clostridium difficile. Nature 458, 1176-1179 (2009).
13. Kuehne, S. A. et al. The role of toxin A and toxin B in Clostridium difficile infection. Nature 467, 711-713 (2010).
14. Carter, G. P. et al. Defining the roles of TcdA and TcdB in localized gastrointestinal disease, systemic organ damage, and the host response during Clostridium difficile infections. MBio 6, e00551 (2015).
15. Hamm, E. E., Voth, D. E., Ballard, J. D. Identification of Clostridium difficile toxin B cardiotoxicity using a zebrafish embryo model of intoxication. Proc. Natl Acad. Sci. USA 103, 14176-14181 (2006).
16. Yuan, P. et al. Chondroitin sulfate proteoglycan 4 functions as the cellular receptor for Clostridium difficile toxin B. Cell Res. 25, 157-168 (2015).
17. Terada, N. et al. Immunohistochemical study of NG2 chondroitin sulfate proteoglycan expression in the small and large intestines. Histochem. Cell Biol. 126, 483-490 (2006).
18. LaFrance, M. E. et al. Identification of an epithelial cell receptor responsible for Clostridium difficile TcdB-induced cytotoxicity. Proc. Natl Acad. Sci. USA 112, 7073-7078 (2015).
19. Shalem, O. et al. Genome-scale CRISPR-Cas9 knockout screening in human cells. Science 343, 84-87 (2014).
20. Doudna, J. A., Charpentier, E. The new frontier of genome engineering with CRISPR-Cas9. Science 346, 1258096 (2014).
21. Greco, A. et al. Carbohydrate recognition by Clostridium difficile toxin A. Nature Struct. Mol. Biol. 13, 460-461 (2006).
22. Barroso, L. A., Moncrief, J. S., Lyerly, D. M., Wilkins, T. D. Mutagenesis of the Clostridium difficile toxin B gene and effect on cytotoxic activity. Microb. Pathog. 16, 297-303 (1994).
23. Genisyuerek, S. et al. Structural determinants for membrane insertion, pore formation and translocation of Clostridium difficile toxin B. Mol. Microbiol. 79, 1643-1654 (2011).
24. Olling, A. et al. The repetitive oligopeptide sequences modulate cytopathic potency but are not crucial for cellular uptake of Clostridium difficile toxin A. PLoS ONE 6, e17623 (2011).
25. Schorch, B. et al. LRP1 is a receptor for Clostridium perfringens TpeL toxin indicating a two-receptor model of clostridial glycosylating toxins. Proc. Natl Acad. Sci. USA 111, 6431-6436 (2014).
26. Ryder, A. B. et al. Assessment of Clostridium difficile infections by quantitative detection of tcdB toxin by use of a real-time cell analysis system. J. Clin. Microbiol. 48, 4129-4134 (2010).
27. Flores-Diáz, M. et al. Cellular UDP-glucose deficiency caused by a single point mutation in the UDP-glucose pyrophosphorylase gene. J. Biol. Chem. 272, 23784-23791 (1997).
28. Chaves-Olarte, E. et al. UDP-glucose deficiency in a mutant cell line protects against glucosyltransferase toxins from Clostridium difficile and Clostridium sordellii. J. Biol. Chem. 271, 6925-6932 (1996).
29. MacDonald, B. T., He, X. Frizzled and LRP5/6 receptors for Wnt/-catenin signaling. Cold Spring Harb. Perspect. Biol. 4, a007880 (2012).
30. Gregorieff, A., Clevers, H. Wnt signaling in the intestinal epithelium: from endoderm to cancer. Genes Dev. 19, 877-890 (2005).
31. Jonikas, M. C. et al. Comprehensive characterization of genes required for protein folding in the endoplasmic reticulum. Science 323, 1693-1697 (2009).
32. Christianson, J. C. et al. Defining human ERAD networks through an integrative mapping strategy. Nature Cell Biol. 14, 93-105 (2011).
33. Orth, P. et al. Mechanism of action and epitopes of Clostridium difficile toxin B-neutralizing antibody bezlotoxumab revealed by X-ray crystallography. J. Biol. Chem. 289, 18008-18021 (2014).
34. Sagara, N., Toda, G., Hirai, M., Terada, M., Katoh, M. Molecular cloning, differential expression, and chromosomal localization of human Frizzled-1, Frizzled-2, and Frizzled-7. Biochem. Biophys. Res. Commun. 252, 117-122 (1998).
35. Richard, M., Boulin, T., Robert, V. J., Richmond, J. E., Bessereau, J. L. Biosynthesis of ionotropic acetylcholine receptors requires the evolutionarily conserved ER membrane complex. Proc. Natl Acad. Sci. USA 110, E1055-E1063 (2013).
36. Satoh, T., Ohba, A., Liu, Z., Inagaki, T., Satoh, A. K. dPob/EMC is essential for biosynthesis of rhodopsin and other multi-pass membrane proteins in Drosophila photoreceptors. eLife 4, e06306 (2015).
37. Ueno, K. et al. Frizzled-7 as a potential therapeutic target in colorectal cancer. Neoplasia 10, 697-705 (2008).
38. Sato, T. et al. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 459, 262-265 (2009).
39. Flanagan, D. J. et al. Frizzled7 functions as a Wnt receptor in intestinal epithelial Lgr5+ stem cells. Stem Cell Reports 4, 759-767 (2015).
40. Yu, H., Ye, X., Guo, N., Nathans, J. Frizzled 2 and Frizzled 7 function redundantly in convergent extension and closure of the ventricular septum and palate: evidence for a network of interacting genes. Development 139, 4383-4394 (2012).
41. Powell, D. W. et al. Myofibroblasts. II. Intestinal subepithelial myofibroblasts. Am. J. Physiol. 277, C183-C201 (1999).
42. Qa'Dan, M., Spyres, L. M., Ballard, J. D. pH-induced conformational changes in Clostridium difficile toxin B. Infect. Immun. 68, 2470-2474 (2000).
43. Pfeifer, G. et al. Cellular uptake of Clostridium difficile toxin B. Translocation of the N-terminal catalytic domain into the cytosol of eukaryotic cells. J. Biol. Chem. 278, 44535-44541 (2003).
44. Bezerra Lima, B. et al. Clostridium difficile toxin A attenuates Wnt/-catenin signaling in intestinal epithelial cells. Infect. Immun. 82, 2680-2687 (2014).
45. Crosnier, C., Stamataki, D., Lewis, J. Organizing cell renewal in the intestine: stem cells, signals and combinatorial control. Nature Rev. Genet. 7, 349-359 (2006).
46. Gujral, T. S. et al. A noncanonical Frizzled2 pathway regulates epithelialmesenchymal transition and metastasis. Cell 159, 844-856 (2014).
47. Hsieh, J. C., Rattner, A., Smallwood, P. M., Nathans, J. Biochemical characterization of Wnt-Frizzled interactions using a soluble, biologically active vertebrate Wnt protein. Proc. Natl Acad. Sci. USA 96, 3546-3551 (1999).
48. Dong, M. et al. Synaptotagmins I and II mediate entry of botulinum neurotoxin B into cells. J. Cell Biol. 162, 1293-1303 (2003).
49. Yang, G. et al. Expression of recombinant Clostridium difficile toxin A and B in Bacillus megaterium. BMC Microbiol. 8, 192 (2008).
50. Tillet, E., Ruggiero, F., Nishiyama, A., Stallcup, W. B. The membrane-spanning proteoglycan NG2 binds to collagens V and VI through the central nonglobular domain of its core protein. J. Biol. Chem. 272, 10769-10776 (1997).
51. MacDonald, B. T., Yokota, C., Tamai, K., Zeng, X., He, X. Wnt signal amplification via activity, cooperativity, and regulation of multiple intracellular PPPSP motifs in the Wnt co-receptor LRP6. J. Biol. Chem. 283, 16115-16123 (2008).
52. Miyoshi, H., Stappenbeck, T. S. In vitro expansion and genetic modification of gastrointestinal stem cells in spheroid culture. Nature Protocols 8, 2471-2482 (2013).
53. Wang, N. et al. Adenovirus-mediated efficient gene transfer into cultured three-dimensional organoids. PLoS ONE 9, e93608 (2014).
54. Grabinger, T. et al. Ex vivo culture of intestinal crypt organoids as a model system for assessing cell death induction in intestinal epithelial cells and enteropathy. Cell Death Dis. 5, e1228 (2014).