CDPK2A and CDPK1 form a signaling module upstream of Toxoplasma motility

CDPK2A和CDPK1形成弓形虫运动上游的信号模块

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作者:Emily Shortt, Caroline G Hackett, Rachel V Stadler, Robyn S Kent, Alice L Herneisen, Gary E Ward, Sebastian Lourido

Abstract

This work uncovers interactions between various signaling pathways that govern Toxoplasma gondii egress. Specifically, we compare the function of three canonical calcium-dependent protein kinases (CDPKs) using chemical-genetic and conditional-depletion approaches. We describe the function of a previously uncharacterized CDPK, CDPK2A, in the Toxoplasma lytic cycle, demonstrating that it contributes to parasite fitness through regulation of microneme discharge, gliding motility, and egress from infected host cells. Comparison of analog-sensitive kinase alleles and conditionally depleted alleles uncovered epistasis between CDPK2A and CDPK1, implying a partial functional redundancy. Understanding the topology of signaling pathways underlying key events in the parasite life cycle can aid in efforts targeting kinases for anti-parasitic therapies.

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