The Toxoplasma dense granule proteins GRA17 and GRA23 mediate the movement of small molecules between the host and the parasitophorous vacuole

Daniel Gold, Aaron D. Kaplan, Agnieszka Lis, Glenna C.L. Bett, Emily E. Rosowski, Kimberly M. Cirelli, Alexandre Bougdour, Saima M. Sidik, Josh R. Beck, Sebastian Lourido, Pascal F. Egea, Peter J. Bradley, Mohamed Ali Hakimi, Randall L. Rasmusson, Jeroen Saeij

Research output: Contribution to journalArticle

86 Scopus citations

Abstract

Toxoplasma gondii is a protozoan pathogen in the phylum Apicomplexa that resides within an intracellular parasitophorous vacuole (PV) that is selectively permeable to small molecules through unidentified mechanisms. We have identified GRA17 as a Toxoplasma-secreted protein that localizes to the parasitophorous vacuole membrane (PVM) and mediates passive transport of small molecules across the PVM. GRA17 is related to the putative Plasmodium translocon protein EXP2 and conserved across PV-residing Apicomplexa. The PVs of GRA17-deficient parasites have aberrant morphology, reduced permeability to small molecules, and structural instability. GRA17-deficient parasites proliferate slowly and are avirulent in mice. These GRA17-deficient phenotypes are rescued by complementation with Plasmodium EXP2. GRA17 functions synergistically with a related protein, GRA23. Exogenous expression of GRA17 or GRA23 alters the membrane conductance properties of Xenopus oocytes in a manner consistent with a large non-selective pore. Thus, GRA17 and GRA23 provide a molecular basis for PVM permeability and nutrient access.

Original languageEnglish (US)
Pages (from-to)642-652
Number of pages11
JournalCell Host and Microbe
Volume17
Issue number5
DOIs
StatePublished - May 13 2015
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Immunology and Microbiology(all)
  • Cancer Research

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    Gold, D., Kaplan, A. D., Lis, A., Bett, G. C. L., Rosowski, E. E., Cirelli, K. M., Bougdour, A., Sidik, S. M., Beck, J. R., Lourido, S., Egea, P. F., Bradley, P. J., Hakimi, M. A., Rasmusson, R. L., & Saeij, J. (2015). The Toxoplasma dense granule proteins GRA17 and GRA23 mediate the movement of small molecules between the host and the parasitophorous vacuole. Cell Host and Microbe, 17(5), 642-652. https://doi.org/10.1016/j.chom.2015.04.003