Journal Article

PP1 phosphatase controls both daughter cell formation and amylopectin levels in Toxoplasma gondii

Guerrera, Ida Chiara, De Souza, Wanderley, Attias, Marcia, Boissavy, Tom, Gissot, Mathieu, Chhuon, Cerina, Khelifa, Asma Sarah, Mouveaux, Thomas, Silva, Tatiana Araujo, Dauvillee, David, Roger, Emmanuel, Bhaskaran, Maanasa

2024

Overview

Virulence of apicomplexan parasites is based on their ability to divide rapidly to produce significant biomass. The regulation of their cell cycle is therefore key to their pathogenesis. Phosphorylation is a crucial posttranslational modification that regulates many aspects of the eukaryotic cell cycle. The phosphatase PP1 is known to play a major role in the phosphorylation balance in eukaryotes. We explored the role of TgPP1 during the cell cycle of the tachyzoite form of the apicomplexan parasite Toxoplasma gondii . Using a conditional mutant strain, we show that TgPP1 regulates many aspects of the cell cycle including the proper assembly of the daughter cells’ inner membrane complex (IMC), the segregation of organelles, and nuclear division. Unexpectedly, depletion of TgPP1 also results in the accumulation of amylopectin, a storage polysaccharide that is usually found in the latent bradyzoite form of the parasite. Using transcriptomics and phospho-proteomics, we show that TgPP1 mainly acts through posttranslational mechanisms by dephosphorylating target proteins including IMC proteins. TgPP1 also dephosphorylates a protein bearing a starch-binding domain. Mutagenesis analysis reveals that the targeted phospho-sites are linked to the ability of the parasite to regulate amylopectin steady-state levels. Therefore, we show that TgPP1 has pleiotropic roles during the tachyzoite cell cycle regulation, but also regulates amylopectin accumulation.

• Publisher: Public Library of Science
• Subject: Accumulation / Amylopectin / Amylopectin - metabolism / Animals / Biochemistry / Biochemistry, Molecular Biology / Cell Cycle / Cell division / Conditional mutant / CRISPR / Cysts / Eukaryotes / Fibroblasts / Genomics / Humans / Kinases / Life Sciences / Microbiological research / Microbiology and Parasitology / Motility / Mutagenesis / Nuclear division / Organelles / Parasites / Parasitology / Pathogenesis / Phosphatase / Phosphatases / Phosphorylation / Physiological aspects / Polysaccharides / Protein Phosphatase 1 - genetics / Protein Phosphatase 1 - metabolism / Proteins / Proteomics / Protozoa / Protozoan Proteins - genetics / Protozoan Proteins - metabolism / Toxoplasma / Toxoplasma - enzymology / Toxoplasma - genetics / Toxoplasma - metabolism / Toxoplasma gondii / Toxoplasmosis / Transcriptomics / Virulence