CDPK2A and CDPK1 form a signaling module upstream of Toxoplasma motility
Name
shortt-et-al-2023-cdpk2a-and-cdpk1-form-a-signaling-module-upstream-of-toxoplasma-motility.pdf
Description
Published version
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2.35 MB
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Checksum (MD5)
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Author(s)
Shortt, Emily
Hackett, Caroline G
Stadler, Rachel V
Kent, Robyn S
Herneisen, Alice L
Ward, Gary E
Lourido, Sebastian
Date Issued
August 23, 2023
Journal
mBio
Publisher
American Society for Microbiology
Citation
Shortt E, Hackett CG, Stadler RV, Kent RS, Herneisen AL, Ward GE, Lourido S. 2023. CDPK2A and CDPK1 form a signaling module upstream of Toxoplasma motility. mBio 14:e01358-23.
Version
Final published version
Abstract
In apicomplexan parasites, the transition between replication and dissemination is regulated by fluctuations in cytosolic calcium concentrations, transduced in part by calcium-dependent protein kinases (CDPKs). We examined the role of CDPK2A in the lytic cycle of Toxoplasma, analyzing its role in the regulation of cellular processes associated with parasite motility. We used chemical-genetic approaches and conditional depletion to determine that CDPK2A contributes to the initiation of parasite motility through microneme discharge. We demonstrate that the N-terminal extension of CDPK2A is necessary for the protein’s function. Conditional depletion revealed an epistatic interaction between CDPK2A and CDPK1, suggesting that the two kinases work together to mediate motility in response to certain stimuli. This signaling module appears distinct from that of CDPK3 and protein kinase G, which also control egress. CDPK2A is revealed as an important regulator of the Toxoplasma kinetic phase, linked to other kinases that govern this critical transition. Our work uncovers extensive interconnectedness between the signaling pathways that regulate parasite motility.
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DOI of Published Version
https://doi.org/10.1128/mbio.01358-23
