Loss of the conserved alveolate kinase MAPK2 decouples toxoplasma cell growth from cell division

Xiaoyu Hu, William J. O’shaughnessy, Tsebaot G. Beraki, Michael L. Reese

Research output: Contribution to journalArticlepeer-review

Abstract

Mitogen-activated protein kinases (MAPKs) are a conserved family of protein kinases that regulate signal transduction, proliferation, and development throughout eukaryotes. The apicomplexan parasite Toxoplasma gondii expresses three MAPKs. Two of these, extracellular signal-regulated kinase 7 (ERK7) and MAPKL1, have been implicated in the regulation of conoid biogenesis and centro-some duplication, respectively. The third kinase, MAPK2, is specific to and conserved throughout the Alveolata, although its function is unknown. We used the auxin-inducible degron system to determine phenotypes associated with MAPK2 loss of function in Toxoplasma. We observed that parasites lacking MAPK2 failed to dupli-cate their centrosomes and therefore did not initiate daughter cell budding, which ultimately led to parasite death. MAPK2-deficient parasites initiated but did not complete DNA replication and arrested prior to mitosis. Surprisingly, the parasites contin-ued to grow and replicate their Golgi apparatus, mitochondria, and apicoplasts. We found that the failure in centrosome duplication is distinct from the phenotype caused by the depletion of MAPKL1. As we did not observe MAPK2 localization at the centrosome at any point in the cell cycle, our data suggest that MAPK2 regulates a process at a distal site that is required for the completion of centrosome duplication and the initiation of parasite mitosis. IMPORTANCE Toxoplasma gondii is a ubiquitous intracellular protozoan parasite that can cause severe and fatal disease in immunocompromised patients and the devel-oping fetus. Rapid parasite replication is critical for establishing a productive infec-tion. Here, we demonstrate that a Toxoplasma protein kinase called MAPK2 is conserved throughout the Alveolata and essential for parasite replication. We found that parasites lacking MAPK2 protein were defective in the initiation of daughter cell budding and were rendered inviable. Specifically, T. gondii MAPK2 (TgMAPK2) ap-pears to be required for centrosome replication at the basal end of the nucleus, and its loss causes arrest early in parasite division. MAPK2 is unique to the Alveolata and not found in metazoa and likely is a critical component of an essential parasite-specific signaling network.

Original languageEnglish (US)
Article numbere02517-20
Pages (from-to)1-18
Number of pages18
JournalmBio
Volume11
Issue number6
DOIs
StatePublished - Nov 1 2020

Keywords

  • Apicomplexan parasites
  • Apicoplast
  • Cell cycle checkpoints
  • Centrosomes
  • Kinase
  • MAP kinases
  • Mitochondria
  • Organelles
  • Toxoplasma gondii

ASJC Scopus subject areas

  • Microbiology
  • Virology

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