Divergent Plasmodium actin residues are essential for filament localization, mosquito salivary gland invasion and malaria transmission

• Verfasst von: Yee, Michelle [VerfasserIn]
• Verfasst von: Walther, Tobias [VerfasserIn]
• Verfasst von: Frischknecht, Friedrich [VerfasserIn]
• Verfasst von: Douglas, Ross G. [VerfasserIn]
• Titel: Divergent Plasmodium actin residues are essential for filament localization, mosquito salivary gland invasion and malaria transmission
• Verf.angabe: Michelle Yee, Tobias Walther, Friedrich Frischknecht, Ross G. Douglas
• E-Jahr: 2022
• Jahr: August 23, 2022
• Umfang: 27 S.
• Fussnoten: Gesehen am 29.03.2023
• Titel Quelle: Enthalten in: Public Library of SciencePLoS pathogens
• Ort Quelle: Lawrence, Kan. : PLoS, 2005
• Jahr Quelle: 2022
• Band/Heft Quelle: 18(2022), 8 vom: Aug., Artikel-ID e1010779, Seite 1-27
• ISSN Quelle: 1553-7374
• DOI: doi:10.1371/journal.ppat.1010779
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Actin filaments
• Sach-SW: Actins
• Sach-SW: Dynamic actin filaments
• Sach-SW: Parasitic diseases
• Sach-SW: Parasitic life cycles
• Sach-SW: Plasmodium
• Sach-SW: Salivary glands
• Sach-SW: Sporozoites
• K10plus-PPN: 1840463066

Abstract

Actin is one of the most conserved and ubiquitous proteins in eukaryotes. Its sequence has been highly conserved for its monomers to self-assemble into filaments that mediate essential cell functions such as trafficking, cell shape and motility. The malaria-causing parasite, Plasmodium, expresses a highly sequence divergent actin that is critical for its rapid motility at different stages within its mammalian and mosquito hosts. Each of Plasmodium actin’s four subdomains have divergent regions compared to canonical vertebrate actins. We previously identified subdomains 2 and 3 as providing critical contributions for parasite actin function as these regions could not be replaced by subdomains of vertebrate actins. Here we probed the contributions of individual divergent amino acid residues in these subdomains on parasite motility and progression. Non-lethal changes in these subdomains did not affect parasite development in the mammalian host but strongly affected progression through the mosquito with striking differences in transmission to and through the insect. Live visualization of actin filaments showed that divergent amino acid residues in subdomains 2 and 4 enhanced localization associated with filaments, while those in subdomain 3 negatively affected actin filaments. This suggests that finely tuned actin dynamics are essential for efficient organ entry in the mosquito vector affecting malaria transmission. This work provides residue level insight on the fundamental requirements of actin in highly motile cells.