A plasma membrane localized protein phosphatase in Toxoplasma gondii, PPM5C, regulates attachment to host cells

Chunlin Yang, Malgorzata Broncel, Caia Dominicus, Emily Sampson, William J. Blakely, Moritz Treeck, Gustavo Arrizabalaga

Research output: Contribution to journalArticle

Abstract

The propagation of Toxoplasma gondii is accomplished by repeated lytic cycles of parasite attachment to a host cell, invasion, replication within a parasitophorous vacuole, and egress from the cell. This lytic cycle is delicately regulated by calcium-dependent reversible phosphorylation of the molecular machinery that drives invasion and egress. While much progress has been made elucidating the protein kinases and substrates central to parasite propagation, little is known about the relevant protein phosphatases. In this study, we focused on the five protein phosphatases that are predicted to be membrane-associated either integrally or peripherally. We have determined that of these only PPM5C, a PP2C family member, localizes to the plasma membrane of Toxoplasma. Disruption of PPM5C results in a slow propagation phenotype in tissue culture. Interestingly, parasites lacking PPM5C divide and undergo egress at a normal rate, but have a deficiency in attaching to host cells. Both membrane localization and phosphatase activity are required for PPM5C’s role in attachment. Phosphoproteomic analysis show relatively few phosphorylation sites being affected by PPM5C deletion in extracellular parasites of which several are found on proteins involved in signaling cascades. This implies that PPM5C is part of a wider regulatory network important for attachment to host cells.

Original languageEnglish (US)
Article number5924
JournalScientific Reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

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Phosphoprotein Phosphatases
Toxoplasma
Blood Proteins
Membrane Proteins
Parasites
Cell Membrane
Phosphorylation
Membranes
Vacuoles
Phosphoric Monoester Hydrolases
Protein Kinases
Calcium
Phenotype
Proteins

ASJC Scopus subject areas

  • General

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A plasma membrane localized protein phosphatase in Toxoplasma gondii, PPM5C, regulates attachment to host cells. / Yang, Chunlin; Broncel, Malgorzata; Dominicus, Caia; Sampson, Emily; Blakely, William J.; Treeck, Moritz; Arrizabalaga, Gustavo.

In: Scientific Reports, Vol. 9, No. 1, 5924, 01.12.2019.

Research output: Contribution to journalArticle

Yang, Chunlin ; Broncel, Malgorzata ; Dominicus, Caia ; Sampson, Emily ; Blakely, William J. ; Treeck, Moritz ; Arrizabalaga, Gustavo. / A plasma membrane localized protein phosphatase in Toxoplasma gondii, PPM5C, regulates attachment to host cells. In: Scientific Reports. 2019 ; Vol. 9, No. 1.
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