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The moving junction protein RON4, although not critical, facilitates host cell invasion and stabilizes MJ members

Published online by Cambridge University Press:  30 June 2017

MING WANG ,
SHINUO CAO ,
NALI DU ,
JIAWEN FU ,
ZHAORAN LI ,
HONGLIN JIA  and
MINGXIN SONG
MING WANG
Affiliation:
College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, China State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang, China
SHINUO CAO
Affiliation:
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang, China
NALI DU
Affiliation:
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang, China
JIAWEN FU
Affiliation:
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang, China
ZHAORAN LI
Affiliation:
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang, China
HONGLIN JIA*
Affiliation:
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang, China
MINGXIN SONG*
Affiliation:
College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, China
*
*Corresponding authors: College of Veterinary Medicine, Northeast Agricultural University, Mucai Street 59, Xiangfang District, Harbin 150001, P.R. China. E-mail: [email protected] and State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Haping Road 678, Xiangfang District, Harbin 150001, P.R. China. E-mail: [email protected]
*Corresponding authors: College of Veterinary Medicine, Northeast Agricultural University, Mucai Street 59, Xiangfang District, Harbin 150001, P.R. China. E-mail: [email protected] and State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Haping Road 678, Xiangfang District, Harbin 150001, P.R. China. E-mail: [email protected]
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Summary

Toxoplasma gondii is an obligate intracellular parasite of phylum Apicomplexa. To facilitate high-efficiency invasion of host cells, T. gondii secretes various proteins related to the moving junction (MJ) complex from rhoptries and micronemes into the interface between the parasite and host. AMA1/RON2/4/5/8 is an important MJ complex, but its mechanism of assembly remains unclear. In this study, we used the CRISPR-Cas9 system to generate a derivative of T. gondii strain RH with a null mutation in TgRON4, thought to be an essential MJ component. Deficiency of TgRON4 moderately decreased invasion ability relative to that of the wild-type parasite. In addition, expression of the endogenous N-terminal fragment of RON5 decreased in the mutant. Together, the results improve our understanding of the assembly mechanism of the MJ complex of T. gondii and raise the possibility of developing new therapeutic drugs that target this complex.

Keywords

TgRON4Toxoplasma gondiiknockoutMJ complex
Type
Research Article
Information
Parasitology , Volume 144 , Issue 11 , September 2017 , pp. 1490 - 1497
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Copyright
Copyright © Cambridge University Press 2017 

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References

REFERENCES

Alexander, D. L., Mital, J., Ward, G. E., Bradley, P. and Boothroyd, J. C. (2005). Identification of the moving junction complex of Toxoplasma gondii: a collaboration between distinct secretory organelles. PLoS Pathogens 1, e17.Google Scholar
Arling, T. A., Yolken, R. H., Lapidus, M., Langenberg, P., Dickerson, F. B., Zimmerman, S. A., Balis, T., Cabassa, J. A., Scrandis, D. A., Tonelli, L. H. and Postolache, T. T. (2009). Toxoplasma gondii antibody titers and history of suicide attempts in patients with recurrent mood disorders. Journal of Nervous and Mental Disease 197, 905–908.Google Scholar
Beck, J. R., Chen, A. L., Kim, E. W. and Bradley, P. J. (2014). RON5 is critical for organization and function of the toxoplasma moving junction complex. PLoS Pathogens 10, e1004025.Google Scholar
Besteiro, S., Michelin, A., Poncet, J., Dubremetz, J. F. and Lebrun, M. (2009). Export of a Toxoplasma gondii rhoptry neck protein complex at the host cell membrane to form the moving junction during invasion. PLoS Pathogens 2, e1000309.Google Scholar
Besteiro, S., Dubremetz, J. F. and Lebrun, M. (2011). The moving junction of apicomplexan parasites: a key structure for invasion. Cell Microbiology 6, 797–805.Google Scholar
Boothroyd, J. C. and Dubremetz, J. F. (2008). Kiss and spit: the dual roles of Toxoplasma rhoptries . Nature Reviews Microbiology 6, 79–88.Google Scholar
Giovannini, D., Späth, S., Lacroix, C., Perazzi, A., Bargieri, D., Lagal, V., Lebugle, C., Combe, A., Thiberge, S., Baldacci, P., Tardieux, I. and Ménard, R. (2011). Independent roles of apical membrane antigen 1 and rhoptry neck proteins during host cell invasion by apicomplexa. Cell Host Microbe 10, 591–602.Google Scholar
Lamarque, M., Besteiro, S., Papoin, J., Roques, M., Vulliez-Le Normand, B., Morlon-Guyot, J., Dubremetz, J. F., Fauquenoy, S., Tomavo, S., Faber, B. W., Kocken, C. H., Thomas, A. W., Boulanger, M. J., Bentley, G. A. and Lebrun, M. (2011). The RON2-AMA1 interaction is a critical step in moving junction-dependent invasion by apicomplexan parasites. PLoS Pathogens 7, e1001276.Google Scholar
Lamarque, M. H., Roques, M., Kong-Hap, M., Tonkin, M. L., Rugarabamu, G., Marq, J. B., Penarete-Vargas, D. M., Boulanger, M. J., Soldati-Favre, D. and Lebrun, M. (2014). Plasticity and redundancy among AMA-RON pairs ensure host cell entry of Toxoplasma parasites. Nature Communications 5, 4098.Google Scholar
Lebrun, M., Michelin, A., El Hajj, H., Poncet, J., Bradley, P. J., Vial, H. and Dubremetz, J. F. (2005). The rhoptry neck protein RON4 re-localizes at the moving junction during Toxoplasma gondii invasion. Cellular Microbiology 7, 1823–1833.Google Scholar
Ling, V. J., Lester, D., Mortensen, P. B., Langenberg, P. W. and Postolache, T. T. (2011). Toxoplasma gondii seropositivity and suicide rates in women. Journal of Nervous and Mental Disease 199, 440–444.Google Scholar
Okusaga, O., Langenberg, P., Sleemi, A., Vaswani, D., Giegling, I., Hartmann, A. M., Konte, B., Friedl, M., Groer, M. W., Yolken, R. H., Rujescu, D. and Postolache, T. T. (2011). Toxoplasma gondii antibody titers and history of suicide attempts in patients with schizophrenia. Schizophrenia Research 133, 150–155.Google Scholar
Parker, M. L., Penarete-Vargas, D. M., Hamilton, P. T., Guérin, A., Dubey, J. P., Perlman, S. J., Spano, F., Lebrun, M. and Boulanger, M. J. (2016). Dissecting the interface between apicomplexan parasite and host cell: insights from a divergent AMA-RON2 pair. Proceedings of the National Academy of Sciences of the USA 113, 398–403.Google Scholar
Poukchanski, A., Fritz, H. M., Tonkin, M. L., Treeck, M., Boulanger, M. J. and Boothroyd, J. C. (2013). Toxoplasma gondii sporozoites invade host cells using two novel paralogues of RON2 and AMA1. PLoS ONE 8, e70637.Google Scholar
Rashid, I., Hedhli, D., Moiré, N., Pierre, J., Debierre-Grockiego, F., Dimier-Poisson, I. and Mévélec, M. N. (2011). Immunological responses induced by a DNA vaccine expressing RON4 and by immunogenic recombinant protein RON4 failed to protect mice against chronic toxoplasmosis. Vaccine 29, 8838–8846.Google Scholar
Shen, B., Brown, K. M., Lee, T. D. and Sibley, L. D. (2014). Efficient gene disruption in diverse strains of Toxoplasma gondii using CRISPR/CAS9. MBio 5, e01114–01114.Google Scholar
Srinivasan, P., Yasgar, A., Luci, D. K., Beatty, W. L., Hu, X., Andersen, J., Narum, D. L., Moch, J. K., Sun, H., Haynes, J. D., Maloney, D. J., Jadhav, A., Simeonov, A. and Miller, L. H. (2013). Disrupting malaria parasite AMA1-RON2 interaction with a small molecule prevents erythrocyte invasion. Nature Communications 4, 2261.Google Scholar
Straub, K. W., Peng, E. D., Hajagos, B. E., Tyler, J. S. and Bradley, P. J. (2011). The moving junction protein RON8 facilitates firm attachment and host cell invasion in Toxoplasma gondii . PLoS Pathogens 7, e1002007.CrossRefGoogle ScholarPubMed
Takemae, H., Sugi, T., Kobayashi, K., Gong, H., Ishiwa, A., Recuenco, F. C., Murakoshi, F., Iwanaga, T., Inomata, A., Horimoto, T., Akashi, H. and Kato, K. (2013). Characterization of the interaction between Toxoplasma gondii rhoptry neck protein 4 and host cellular beta-tubulin. Scientific Reports 3, 3199.Google Scholar
Tyler, J. S. and Boothroyd, J. C. (2011). The C-terminus of Toxoplasma RON2 provides the crucial link between AMA1 and the host-associated invasion complex. PLoS Pathogens 7, e1001282.Google Scholar
Zheng, J., Jia, H. and Zheng, Y. (2015). Knockout of leucine aminopeptidase in Toxoplasma gondii using CRISPR/Cas9. International Journal for Parasitology 45, 141–148.Google Scholar
Zheng, J., Cheng, Z., Jia, H. and Zheng, Y. (2016). Characterization of aspartyl aminopeptidase from Toxoplasma gondii . Scientific Reports 6, 34448.CrossRefGoogle ScholarPubMed
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