Plasmodium rootlet SFA1 coordinates cell replication, apical polarity and cytoskeletal organisation during sexual development

Brady, D.; Mishra, A.; Ilani, P.; Ferguson, D. J. P.; Ubiaru, P.; Markus, R.; Bottrill, A.; Zeeshan, M.; Vaughan, S.; Guttery, D. S.; Tromer, E. C.; Holder, A. A.; Tewari, R.

doi:10.64898/2026.10.30.761637

bioRxiv · 10.64898/2026.10.30.761637

Plasmodium rootlet SFA1 coordinates cell replication, apical polarity and cytoskeletal organisation during sexual development

Brady, D.·Mishra, A.·Ilani, P.·Ferguson, D. J. P.·Ubiaru, P.·Markus, R.·Bottrill, A.·Zeeshan, M.·Vaughan, S.·Guttery, D. S.·Tromer, E. C.·Holder, A. A.·Tewari, R.

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Abstract

Rootlet fibres are evolutionarily conserved cytoskeletal structures involved in basal body positioning and cytoskeletal organisation in diverse eukaryotes. Plasmodium spps, undergo complex developmental transitions that require precise coordination of cell polarity, cytoskeletal remodelling and nuclear division. In Plasmodium striated fibre assemblin1 (SFA1) and SFA2 have been implicated in linking the centriolar plaque to nascent apical poles during schizogony and sporogony. However, their role in sexual development is unclear. Here we show SFA1 is absent from the male basal body but is present in female gametocytes, where it marks the polarity initiation site during zygote-to-ookinete differentiation. We also identify associations between SFA1, SFA2 and pellicle-associated proteins. Loss of sfa1 disrupts apical polarity, pellicle organisation and subpellicular microtubules, producing abnormal immotile ookinetes and affecting further sporozoite development, leading to complete loss of parasite transmission. Together, these findings support an important role for SFA1 in organising the cytoskeletal architecture required for malaria transmission.

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Brady, D., Mishra, A., Ilani, P., Ferguson, D. J. P., Ubiaru, P., Markus, R., Bottrill, A., Zeeshan, M., Vaughan, S., Guttery, D. S., Tromer, E. C., Holder, A. A., Tewari, R.. 2026-11-02. Plasmodium rootlet SFA1 coordinates cell replication, apical polarity and cytoskeletal organisation during sexual development. https://doi.org/10.64898/2026.10.30.761637

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