γ-tubulin complex controls the nucleation of tubulin-based structures in Apicomplexa

SUMMARY

Apicomplexan parasites rely on tubulin structures throughout their cell and life cycles, particularly in the polymerization of spindle microtubules to separate the replicated nucleus into daughter cells. Additionally, tubulin structures, including conoid and subpellicular microtubules, provide the necessary rigidity and structure for dissemination and host cell invasion. However, it is unclear whether these tubulin structures are nucleated via a highly conserved γ-tubulin complex or through a specific process unique to apicomplexans. This study, led by GCIR Professor Dominique Soldati-Favre, demonstrates that Toxoplasma γ-tubulin is responsible for nucleating spindle microtubules, akin to higher eukaryotes, facilitating nucleus division in newly formed parasites. Interestingly, γ-tubulin colocalizes with nascent conoid and subpellicular microtubules during division, potentially nucleating these structures as well. Loss of γ-tubulin results in significant morphological defects due to impaired nucleus scission and the loss of conoid and subpellicular microtubule nucleation, crucial for parasite shape and rigidity. Additionally, the nucleation process of tubulin structures involves a concerted action of γ-tubulin and Gamma Tubulin Complex proteins (GCPs), recapitulating the localization and phenotype of γ-tubulin. This study also introduces new molecular markers for cytoskeletal structures and applies iterative expansion microscopy to reveal microtubule-based architecture in Cryptosporidium parvum sporozoites, further demonstrating the conserved localization and probable function of γ-tubulin in Cryptosporidium.

Full article published in Molecular Biology of the Cell: https://doi.org/10.1091/mbc.E24-03-0100

Why is it important?

The Apicomplexa phylum includes thousands of species and among them, some are pathogens responsible for human diseases such as Cryptosporidium (cryptosporidiosis), Plasmodium (malaria) and Toxoplasma gondii (toxoplasmosis). To invade host cells, apicomplexan parasites rely on tubulin-based structures for crucial activities such as movement and reproduction. This research focuses on γ-tubulin, a protein that plays a key role in the formation of these structures. The researchers combined ultrastructure-expansion microscopy (U-ExM) and genome editing to investigate the localisation and function of γ-tubulin. The study demonstrates that γ-tubulin is required to create the spindle microtubules essential for cell division. Without γ-tubulin, these parasites cannot divide properly, leading to severe morphological problems. These findings shed light on the basic biology of these parasites and paves the way for developing new treatments.

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