CoChat
Sign Up
Cited by 46Toxoplasma gondii Research StudiesMicrotubule and mitosis dynamicsCoccidia and coccidiosis research

The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.

Conoid extrusion regulates glideosome assembly to control motility and invasion in Apicomplexa

Open access
Dos Santos Pacheco, Nicolas, Brusini, Lorenzo, Haase, Romuald, Tosetti, Nicolò, Maco, Bohumil, Brochet, Mathieu, Vadas, Oscar, Soldati-Favre, Dominique·2022·Nature Microbiology
DOI 10.1038/s41564-022-01212-x

Published version of a preprint

Open this paper in CoChat — free accountOpen PDF

Abstract

Members of Apicomplexa are defined by apical cytoskeletal structures and secretory organelles, tailored for motility, invasion and egress. Gliding is powered by actomyosin-dependent rearward translocation of apically secreted transmembrane adhesins. In the human parasite Toxoplasma gondii, the conoid, composed of tubulin fibres and preconoidal rings (PCRs), is a dynamic organelle of undefined function. Here, using ultrastructure expansion microscopy, we established that PCRs serve as a hub for glideosome components including Formin1. We also identified components of the PCRs conserved in Apicomplexa, Pcr4 and Pcr5, that contain B-box zinc-finger domains, assemble in heterodimer and are essential for the formation of the structure. The fitness conferring Pcr6 tethers the PCRs to the cone of tubulin fibres. F-actin produced by Formin1 is used by Myosin H to generate the force for conoid extrusion which directs the flux of F-actin to the pellicular space, serving as gatekeeper to control parasite motility.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s41564-022-01212-x

Cites

4 of 4 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 82

  1. Adl, S. M. et al. Diversity, nomenclature, and taxonomy of protists. Syst. Biol. 56, 684–689 (2007). · DOI
  2. Montoya, J. G. & Liesenfeld, O. Toxoplasmosis. Lancet 363, 1965–1976 (2004). · DOI
  3. Phillips, M. A. et al. Malaria. Nat. Rev. Dis. Prim. 3, 17050 (2017). · DOI
  4. Rashid, M. et al. A systematic review on modelling approaches for economic losses studies caused by parasites and their associated diseases in cattle. Parasitology 146, 129–141 (2019). · DOI
  5. Guerin, A. & Striepen, B. The biology of the intestinal intracellular parasite Cryptosporidium. Cell Host Microbe 28, 509–515 (2020). · DOI
  6. Frenal, K., Dubremetz, J. F., Lebrun, M. & Soldati-Favre, D. Gliding motility powers invasion and egress in Apicomplexa. Nat. Rev. Microbiol. 15, 645–660 (2017). · DOI
  7. Gubbels, M. J. & Duraisingh, M. T. Evolution of apicomplexan secretory organelles. Int J. Parasitol. 42, 1071–1081 (2012). · DOI
  8. Dos Santos Pacheco, N., Tosetti, N., Koreny, L., Waller, R. F. & Soldati-Favre, D. Evolution, composition, assembly, and function of the conoid in Apicomplexa. Trends Parasitol. 36, 688–704 (2020). · DOI
  9. D’Haese, J., Mehlhorn, H. & Peters, W. Comparative electron microscope study of pellicular structures in coccidia (Sarcocystis, Besnoitia and Eimeria). Int. J. Parasitol. 7, 505–518 (1977). · DOI
  10. Mann, T. & Beckers, C. J. Characterization of the subpellicular network, a filamentous membrane skeletal component in the parasite Toxoplasma gondii. Mol. Biochem Parasitol. 115, 257–268 (2001). · DOI
  11. Morrissette, N. S. & Sibley, L. D. Cytoskeleton of apicomplexan parasites. Microbiol Mol. Biol. Rev. 66, 21–38 (2002). · DOI
  12. Tran, J. Q. et al. RNG1 is a late marker of the apical polar ring in Toxoplasma gondii. Cytoskeleton (Hoboken) 67, 586–598 (2010). · DOI
  13. Leung, J. M. et al. Stability and function of a putative microtubule-organizing center in the human parasite Toxoplasma gondii. Mol. Biol. Cell 28, 1361–1378 (2017). · DOI
  14. Dubois, D. J. & Soldati-Favre, D. Biogenesis and secretion of micronemes in Toxoplasma gondii. Cell Microbiol. 21, e13018 (2019). · DOI
  15. Ben Chaabene, R., Lentini, G. & Soldati-Favre, D. Biogenesis and discharge of the rhoptries: key organelles for entry and hijack of host cells by the Apicomplexa. Mol. Microbiol. 115, 453–465 (2021). · DOI
  16. Besteiro, S., Michelin, A., Poncet, J., Dubremetz, J. F. & Lebrun, M. Export of a Toxoplasma gondii rhoptry neck protein complex at the host cell membrane to form the moving junction during invasion. PLoS Pathog. 5, e1000309 (2009). · DOI
  17. Jacot, D. et al. An Apicomplexan actin-binding protein serves as a connector and lipid sensor to coordinate motility and invasion. Cell Host Microbe 20, 731–743 (2016). · DOI
  18. Tosetti, N., Dos Santos Pacheco, N., Soldati-Favre, D. & Jacot, D. Three F-actin assembly centers regulate organelle inheritance, cell-cell communication and motility in Toxoplasma gondii. eLife 8, e42669 (2019). · DOI
  19. Daher, W., Plattner, F., Carlier, M. F. & Soldati-Favre, D. Concerted action of two formins in gliding motility and host cell invasion by Toxoplasma gondii. PLoS Pathog. 6, e1001132 (2010). · DOI
  20. Baum, J. et al. A malaria parasite formin regulates actin polymerization and localizes to the parasite-erythrocyte moving junction during invasion. Cell Host Microbe 3, 188–198 (2008). · DOI
  21. Dubremetz, J. F. Rhoptries are major players in Toxoplasma gondii invasion and host cell interaction. Cell Microbiol. 9, 841–848 (2007). · DOI
  22. Frenal, K., Marq, J. B., Jacot, D., Polonais, V. & Soldati-Favre, D. Plasticity between MyoC- and MyoA-glideosomes: an example of functional compensation in Toxoplasma gondii invasion. PLoS Pathog. 10, e1004504 (2014). · DOI
  23. Graindorge, A. et al. The conoid associated motor MyoH is indispensable for Toxoplasma gondii entry and exit from host cells. PLoS Pathog. 12, e1005388 (2016). · DOI
  24. Heaslip, A. T., Nishi, M., Stein, B. & Hu, K. The motility of a human parasite, Toxoplasma gondii, is regulated by a novel lysine methyltransferase. PLoS Pathog. 7, e1002201 (2011). · DOI
  25. Bertiaux, E. et al. Expansion microscopy provides new insights into the cytoskeleton of malaria parasites including the conservation of a conoid. PLoS Biol. 19, e3001020 (2021). · DOI
  26. Koreny, L. et al. Molecular characterization of the conoid complex in Toxoplasma reveals its conservation in all apicomplexans, including Plasmodium species. PLoS Biol. 19, e3001081 (2021). · DOI
  27. Wall, R. J. et al. SAS6-like protein in Plasmodium indicates that conoid-associated apical complex proteins persist in invasive stages within the mosquito vector. Sci. Rep. 6, 28604 (2016). · DOI
  28. Ferreira, J. L. et al. Form follows function: variable microtubule architecture in the malaria parasite. Preprint at bioRxiv https://doi.org/10.1101/2022.04.13.488170 (2022). · DOI
  29. Mondragon, R. & Frixione, E. Ca2+-dependence of conoid extrusion in Toxoplasma gondii tachyzoites. J. Eukaryot. Microbiol 43, 120–127 (1996). · DOI
  30. Monteiro, V. G., de Melo, E. J., Attias, M. & de Souza, W. Morphological changes during conoid extrusion in Toxoplasma gondii tachyzoites treated with calcium ionophore. J. Struct. Biol. 136, 181–189 (2001). · DOI
  31. Del Carmen, M. G., Mondragon, M., Gonzalez, S. & Mondragon, R. Induction and regulation of conoid extrusion in Toxoplasma gondii. Cell Microbiol. 11, 967–982 (2009). · DOI
  32. Hortua Triana, M. A., Marquez-Nogueras, K. M., Vella, S. A. & Moreno, S. N. J. Calcium signaling and the lytic cycle of the Apicomplexan parasite Toxoplasma gondii. Biochim. Biophys. Acta Mol. Cell Res. 1865, 1846–1856 (2018). · DOI
  33. Heaslip, A. T., Ems-McClung, S. C. & Hu, K. TgICMAP1 is a novel microtubule binding protein in Toxoplasma gondii. PLoS ONE 4, e7406 (2009). · DOI
  34. Mageswaran, S. K. et al. In situ ultrastructures of two evolutionarily distant apicomplexan rhoptry secretion systems. Nat. Commun. 12, 4983 (2021). · DOI
  35. Leung, J. M., Liu, J., Wetzel, L. A. & Hu, K. Centrin2 from the human parasite Toxoplasma gondii is required for its invasion and intracellular replication. J. Cell Sci. 132, jcs228791 (2019). · DOI
  36. Dos Santos Pacheco, N. & Soldati-Favre, D. Coupling auxin-inducible degron system with ultrastructure expansion microscopy to accelerate the discovery of gene function in Toxoplasma gondii. Methods Mol. Biol. 2369, 121–137 (2021). · DOI
  37. de Leon, J. C. et al. A SAS-6-like protein suggests that the Toxoplasma conoid complex evolved from flagellar components. Eukaryot. Cell 12, 1009–1019 (2013). · DOI
  38. Long, S., Anthony, B., Drewry, L. L. & Sibley, L. D. A conserved ankyrin repeat-containing protein regulates conoid stability, motility and cell invasion in Toxoplasma gondii. Nat. Commun. 8, 2236 (2017). · DOI
  39. Nagayasu, E., Hwang, Y. C., Liu, J., Murray, J. M. & Hu, K. Loss of a doublecortin (DCX)-domain protein causes structural defects in a tubulin-based organelle of Toxoplasma gondii and impairs host-cell invasion. Mol. Biol. Cell 28, 411–428 (2017). · DOI
  40. Howard, B. L. et al. Identification of potent phosphodiesterase inhibitors that demonstrate cyclic nucleotide-dependent functions in apicomplexan parasites. ACS Chem. Biol. 10, 1145–1154 (2015). · DOI
  41. Hu, K. et al. Cytoskeletal components of an invasion machine–the apical complex of Toxoplasma gondii. PLoS Pathog. 2, e13 (2006). · DOI
  42. Lentini, G., Dubois, D. J., Maco, B., Soldati-Favre, D. & Frenal, K. The roles of Centrin 2 and Dynein Light Chain 8a in apical secretory organelles discharge of Toxoplasma gondii. Traffic 20, 583–600 (2019). · DOI
  43. Hammoudi, P. M., Maco, B., Dogga, S. K., Frenal, K. & Soldati-Favre, D. Toxoplasma gondii TFP1 is an essential transporter family protein critical for microneme maturation and exocytosis. Mol Microbiol. 109, 225–244 (2018). · DOI
  44. Barylyuk, K. et al. A comprehensive subcellular atlas of the Toxoplasma proteome via hyperLOPIT provides spatial context for protein functions. Cell Host Microbe 28, 752–766 e759 (2020). · DOI
  45. Sidik, S. M. et al. A genome-wide CRISPR screen in Toxoplasma identifies essential apicomplexan genes. Cell 166, 1423–1435.e1412 (2016). · DOI
  46. Kluska, K., Adamczyk, J. & Krężel, A. Metal binding properties, stability and reactivity of zinc fingers. Coord. Chem. Rev. 367, 18–64 (2018). · DOI
  47. Munera Lopez, J. et al. An apical protein Pcr2 is required for persistent movement by the human parasite Toxoplasma gondii. PLOS Pathog. 18, e1010776 (2022). · DOI · Paper page
  48. Tosetti, N. et al. Essential function of the alveolin network in the subpellicular microtubules and conoid assembly in Toxoplasma gondii. eLife 9, e56635 (2020). · DOI
  49. Carruthers, V., Giddings, O. K. & Sibley, L. D. Secretion of micronemal proteins is associated with toxoplasma invasion of host cells. Cell. Microbiol. 1, 225–235 (1999). · DOI
  50. Bisio, H., Lunghi, M., Brochet, M. & Soldati-Favre, D. Phosphatidic acid governs natural egress in Toxoplasma gondii via a guanylate cyclase receptor platform. Nat. Microbiol 4, 420–428 (2019). · DOI
  51. Dos Santos Pacheco, N. et al. Revisiting the role of Toxoplasma gondii ERK7 in the maintenance and stability of the apical complex. mBio 12, e0205721 (2021). · DOI
  52. Cassandri, M. et al. Zinc-finger proteins in health and disease. Cell Death Disco. 3, 17071 (2017). · DOI
  53. James, E. I., Murphree, T. A., Vorauer, C., Engen, J. R. & Guttman, M. Advances in hydrogen/deuterium exchange mass spectrometry and the pursuit of challenging biological systems. Chem. Rev. 122, 7562–7623 (2021). · DOI
  54. Bannister, L. H., Hopkins, J. M., Fowler, R. E., Krishna, S. & Mitchell, G. H. Ultrastructure of rhoptry development in Plasmodium falciparum erythrocytic schizonts. Parasitology 121, 273–287 (2000). · DOI
  55. Hanssen, E. et al. Electron tomography of Plasmodium falciparum merozoites reveals core cellular events that underpin erythrocyte invasion. Cell Microbiol. 15, 1457–1472 (2013). · DOI
  56. Bushell, E. et al. Functional profiling of a plasmodium genome reveals an abundance of essential genes. Cell 170, 260–272 e268 (2017). · DOI
  57. Zhang, M. et al. Uncovering the essential genes of the human malaria parasite Plasmodium falciparum by saturation mutagenesis. Science 360, eaap7847 (2018). · DOI
  58. Laurentino, E. C. et al. Experimentally controlled downregulation of the histone chaperone FACT in Plasmodium berghei reveals that it is critical to male gamete fertility. Cell Microbiol. 13, 1956–1974 (2011). · DOI
  59. Nichols, B. A. & Chiappino, M. L. Cytoskeleton of Toxoplasma gondii. J. Protozool. 34, 217–226 (1987). · DOI
  60. Sivagurunathan, S., Heaslip, A., Liu, J. & Hu, K. Identification of functional modules of AKMT, a novel lysine methyltransferase regulating the motility of Toxoplasma gondii. Mol. Biochem. Parasitol. 189, 43–53 (2013). · DOI
  61. Pavlou, G. et al. Coupling polar adhesion with traction, spring, and torque forces allows high-speed helical migration of the protozoan parasite toxoplasma. ACS Nano. 14, 7121–7139 (2020). · DOI
  62. Pavlou, G. et al. Toxoplasma parasite twisting motion mechanically induces host cell membrane fission to complete invasion within a protective vacuole. Cell Host Microbe 24, 81–96 e85 (2018). · DOI
  63. Soldati, D. & Boothroyd, J. Transient transfection and expression in the obligate intracellular parasite Toxoplasma gondii. Science 260, 349–352 (1993). · DOI
  64. Brown, K. M., Long, S. & Sibley, L. D. Plasma membrane association by N-acylation governs PKG function in Toxoplasma gondii. mBio 8, e00375-17 (2017). · DOI
  65. Meissner, M., Brecht, S., Bujard, H. & Soldati, D. Modulation of myosin A expression by a newly established tetracycline repressor-based inducible system in Toxoplasma gondii. Nucleic Acid Res. 29, E115 (2001). · DOI
  66. Billker, O. et al. Calcium and a calcium-dependent protein kinase regulate gamete formation and mosquito transmission in a malaria parasite. Cell 117, 503–514 (2004). · DOI
  67. Fang, H. et al. Epistasis studies reveal redundancy among calcium-dependent protein kinases in motility and invasion of malaria parasites. Nat. Commun. 9, 4248 (2018). · DOI
  68. Brusini, L., Dos Santos Pacheco, N., Tromer, E. C., Soldati-Favre, D. & Brochet, M. Composition and organization of kinetochores show plasticity in apicomplexan chromosome segregation. J. Cell Biol. 221, e202111084 (2022). · DOI
  69. Sebastian, S. et al. A Plasmodium calcium-dependent protein kinase controls zygote development and transmission by translationally activating repressed mRNAs. Cell Host Microbe 12, 9–19 (2012). · DOI
  70. Gurnett, A. M. et al. Purification and molecular characterization of cGMP-dependent protein kinase from Apicomplexan parasites. A novel chemotherapeutic target. J. Biol. Chem. 277, 15913–15922 (2002). · DOI
  71. Plattner, F. et al. Toxoplasma profilin is essential for host cell invasion and TLR11-dependent induction of an interleukin-12 response. Cell Host Microbe 3, 77–87 (2008). · DOI
  72. Sheiner, L. et al. A systematic screen to discover and analyze apicoplast proteins identifies a conserved and essential protein import factor. PLoS Pathog. 7, e1002392 (2011). · DOI
  73. Lentini, G. et al. Structural insights into an atypical secretory pathway kinase crucial for Toxoplasma gondii invasion. Nat. Commun. 12, 3788 (2021). · DOI
  74. Moon, R. W. et al. A cyclic GMP signalling module that regulates gliding motility in a malaria parasite. PLoS Pathog. 5, e1000599 (2009). · DOI
  75. Mathur, V. et al. Multiple independent origins of apicomplexan-like parasites. Curr. Biol. 29, 2936–2941.e5 (2019). · DOI · Paper page
  76. Mathur, V. et al. Phylogenomics identifies a new major subgroup of apicomplexans, marosporida class nov., with extreme apicoplast genome reduction. Genome Biol. Evol. 13, evaa244 (2021). · DOI · Paper page
  77. Katoh, K., Kuma, K., Toh, H. & Miyata, T. MAFFT version 5: improvement in accuracy of multiple sequence alignment. Nucleic Acids Res. 33, 511–518 (2005). · DOI
  78. Eddy, S. R. A new generation of homology search tools based on probabilistic inference. Genome Informatics. International Conference on Genome Informatics 23, 205–211 (2009).
  79. Waterhouse, A. M., Procter, J. B., Martin, D. M., Clamp, M. & Barton, G. J. Jalview Version 2–a multiple sequence alignment editor and analysis workbench. Bioinformatics 25, 1189–1191 (2009). · DOI
  80. Soding, J. Protein homology detection by HMM-HMM comparison. Bioinformatics 21, 951–960 (2005). · DOI
  81. Minh, B. Q. et al. IQ-TREE 2: New models and efficient methods for phylogenetic inference in the genomic era. Mol. Biol. Evol. 37, 1530–1534 (2020). · DOI · Paper page
  82. Revell, L. J. phytools: an R package for phylogenetic comparative biology (and other things). Methods Ecol. Evolution 3, 217–223 (2012). · DOI

Metadata

Authors
Dos Santos Pacheco, N., Brusini, L., Haase, R., Tosetti, N., Maco, B., Brochet, M., Vadas, O., & Soldati-Favre, D.
Affiliations
University of Geneva (CH)
Corresponding author
Vadas, Oscar
ORCID
Venue
Nature Microbiology
Publisher
Springer Science and Business Media LLC
Published
2022-09-15
Volume
7
Issue
11
Pages
1777-1790
ISSN
2058-5276 (ISSN-L)
DOI
10.1038/s41564-022-01212-x
OpenAlex
W4295925642
Cited by
46
References
4
Citations by year
2026: 9 · 2025: 8 · 2024: 18 · 2023: 8 · 2022: 3
FWCI
7.38
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Microbiology (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Archive ouverte UNIGE (University of Geneva) (publishedVersion)
  • Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
Funders
  • Novartis Foundation (19C189)
  • European Commission (HORIZON2020, 695596)
  • École Polytechnique Fédérale de Lausanne
  • Université de Genève
Topics
  • Life Sciences › Immunology and Microbiology › Parasitology › Toxoplasma gondii Research Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Coccidia and coccidiosis research
Keywords
Apicomplexa, Toxoplasma gondii, parasite invasion, egress, ultrastructure expansion microscopy
MeSH terms
Actins, Cytoskeleton, Humans, Toxoplasma, Tubulin, Protozoan Proteins, Apicomplexa

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review