Divergent kinase regulates membrane ultrastructure of the Toxoplasma parasitophorous vacuole

Tsebaot Beraki, Xiaoyu Hu, Malgorzata Broncel, Joanna C. Young, William J O'Shaughnessy, Dominika Borek, M Treeck, ML Reese

Research output: Contribution to journalArticlepeer-review

Abstract

Apicomplexan parasites replicate within a protective organelle, called the parasitophorous vacuole (PV). The Toxoplasma gondii PV is filled with a network of tubulated membranes, which are thought to facilitate trafficking of effectors and nutrients. Despite being critical to parasite virulence, there is scant mechanistic understanding of the network’s functions. Here, we identify the parasite-secreted kinase WNG1 (With-No-Gly-loop) as a critical regulator of tubular membrane biogenesis. WNG1 family members adopt an atypical protein kinase fold lacking the glycine rich ATP-binding loop that is required for catalysis in canonical kinases. Unexpectedly, we find that WNG1 is an active protein kinase that localizes to the PV lumen and phosphorylates PV-resident proteins, several of which are essential for the formation of a functional intravacuolar network. Moreover, we show that WNG1-dependent phosphorylation of these proteins is required for their membrane association, and thus their ability to tubulate membranes. Consequently, WNG1 knockout parasites have an aberrant PV membrane ultrastructure. Collectively, our results describe a unique family of Toxoplasma kinases and implicate phosphorylation of secreted proteins as a mechanism of regulating PV development during parasite infection.
Original languageEnglish
Pages (from-to)6361-6370
Number of pages9
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number13
Early online date8 Mar 2019
DOIs
Publication statusPublished - 26 Mar 2019

Keywords

  • kinase
  • pseudokinase
  • phosphorylation
  • host pathogen interaction
  • chaperone

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