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

  • MING WANG (a1) (a2), SHINUO CAO (a2), NALI DU (a2), JIAWEN FU (a2), ZHAORAN LI (a2), HONGLIN JIA (a2) and MINGXIN SONG (a1)...

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.

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Corresponding author

*Corresponding authors: College of Veterinary Medicine, Northeast Agricultural University, Mucai Street 59, Xiangfang District, Harbin 150001, P.R. China. E-mail: songmx@neau.edu.cn 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: jiahonglin@caas.cn

References

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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.
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, 905908.
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.
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.
Besteiro, S., Dubremetz, J. F. and Lebrun, M. (2011). The moving junction of apicomplexan parasites: a key structure for invasion. Cell Microbiology 6, 797805.
Boothroyd, J. C. and Dubremetz, J. F. (2008). Kiss and spit: the dual roles of Toxoplasma rhoptries . Nature Reviews Microbiology 6, 7988.
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, 591602.
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.
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.
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, 18231833.
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, 440444.
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, 150155.
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, 398403.
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.
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, 88388846.
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, e0111401114.
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.
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.
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.
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.
Zheng, J., Jia, H. and Zheng, Y. (2015). Knockout of leucine aminopeptidase in Toxoplasma gondii using CRISPR/Cas9. International Journal for Parasitology 45, 141148.
Zheng, J., Cheng, Z., Jia, H. and Zheng, Y. (2016). Characterization of aspartyl aminopeptidase from Toxoplasma gondii . Scientific Reports 6, 34448.

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