Toxoplasma gondii arginine methyltransferase 1 (PRMT1) is necessary for centrosome dynamics during tachyzoite cell division

Kamal El Bissati, Elena S. Suvorova, Hui Xiao, Olivier Lucas, Rajendra Upadhya, Yanfen Ma, Ruth Hogue Angeletti, Michael W. White, Louis M. Weiss, Kami Kim

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

The arginine methyltransferase family (PRMT) has been implicated in a variety of cellular processes, including signal transduction, epigenetic regulation, and DNA repair pathways. PRMT1 is thought to be responsible for the majority of PRMT activity in Toxoplasma gondii, but its exact function is unknown. To further define the biological function of the PRMT family, we generated T. gondii mutants lacking PRMT1 (_prmt1) by deletion of the PRMT1 gene. ∆prmt1 parasites exhibit morphological defects during cell division and grow slowly, and this phenotype reverses in the ∆prmt::PRMT1mRFP complemented strain. Tagged PRMT1 localizes primarily in the cytoplasm with enrichment at the pericentriolar material, and the strain lacking PRMT1 is unable to segregate progeny accurately. Unlike wild-type and complemented parasites, ∆prmt1 parasites have abnormal daughter buds, perturbed centrosome stoichiometry, and loss of synchronous replication. Whole-genome expression profiling demonstrated differences in expression of cell-cycle-regulated genes in the ∆prmt1 strain relative to the complemented ∆prmt1::PRMT1mRFP and parental wild-type strains, but these changes do not correlate with a specific block in cell cycle. Although PRMT1’s primary biological function was previously proposed to be methylation of histones, our studies suggest that PRMT1 plays an important role within the centrosome to ensure the proper replication of the parasite. IMPORTANCE Apicomplexan parasites include several important pathogens, including Toxoplasma gondii, a major cause of opportunistic infections and congenital birth defects. These parasites divide using a unique form of cell division called endodyogeny that is different from those of most eukaryotes. PRMT1 is a conserved arginine methyltransferase that was thought to regulate gene expression of T. gondii by modifying histone methylation. Using genetic techniques, we show that disruption of PRMT1 affects the parasite's ability to perform accurate cell division. Our studies reveal an unexpected role for arginine methylation in centrosome biology and regulation of parasite replication.

Original languageEnglish (US)
Article numbere02094-15
JournalmBio
Volume7
Issue number1
DOIs
StatePublished - Feb 2 2016

    Fingerprint

ASJC Scopus subject areas

  • Microbiology
  • Virology

Cite this

El Bissati, K., Suvorova, E. S., Xiao, H., Lucas, O., Upadhya, R., Ma, Y., Angeletti, R. H., White, M. W., Weiss, L. M., & Kim, K. (2016). Toxoplasma gondii arginine methyltransferase 1 (PRMT1) is necessary for centrosome dynamics during tachyzoite cell division. mBio, 7(1), [e02094-15]. https://doi.org/10.1128/mBio.02094-15