title: The Toxoplasma Dense Granule Proteins GRA17 and GRA23 Mediate the Movement of Small Molecules between the Host and the Parasitophorous Vacuole.
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.
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Gold
authors.affiliation: Physiology and Biophysics, The State University of New York, University at Buffalo, Buffalo, NY 14214, USA; Center for Cellular and Systems Electrophysiology, School of Medicine & Biomedical Sciences, The State University of New York, University at Buffalo, Buffalo, NY 14214, USA.
authors.forename: Aaron D
authors.initials: AD
authors.lastname: Kaplan
authors.affiliation: Physiology and Biophysics, The State University of New York, University at Buffalo, Buffalo, NY 14214, USA; Center for Cellular and Systems Electrophysiology, School of Medicine & Biomedical Sciences, The State University of New York, University at Buffalo, Buffalo, NY 14214, USA.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Lis
authors.affiliation: Physiology and Biophysics, The State University of New York, University at Buffalo, Buffalo, NY 14214, USA; Center for Cellular and Systems Electrophysiology, School of Medicine & Biomedical Sciences, The State University of New York, University at Buffalo, Buffalo, NY 14214, USA; Department of Obstetrics and Gynocology, School of Medicine & Biomedical Sciences, The State University of New York, University at Buffalo, Buffalo, NY 14214, USA.
authors.forename: Glenna C L
authors.initials: GC
authors.lastname: Bett
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Emily E
authors.initials: EE
authors.lastname: Rosowski
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Kimberly M
authors.initials: KM
authors.lastname: Cirelli
authors.affiliation: UMR5163, LAPM, Centre National de la Recherche Scientifique, 38041 Grenoble, France; Université Joseph Fourier, 38000 Grenoble, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Bougdour
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
authors.forename: Saima M
authors.initials: SM
authors.lastname: Sidik
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Josh R
authors.initials: JR
authors.lastname: Beck
authors.affiliation: Université Joseph Fourier, 38000 Grenoble, France.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Lourido
authors.affiliation: Department of Biological Chemistry, UCLA David Geffen School of Medicine, Los Angeles, CA 90095, USA.
authors.forename: Pascal F
authors.initials: PF
authors.lastname: Egea
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Bradley
authors.affiliation: UMR5163, LAPM, Centre National de la Recherche Scientifique, 38041 Grenoble, France; Université Joseph Fourier, 38000 Grenoble, France.
authors.forename: Mohamed-Ali
authors.initials: MA
authors.lastname: Hakimi
authors.affiliation: Physiology and Biophysics, The State University of New York, University at Buffalo, Buffalo, NY 14214, USA; Center for Cellular and Systems Electrophysiology, School of Medicine & Biomedical Sciences, The State University of New York, University at Buffalo, Buffalo, NY 14214, USA.
authors.forename: Randall L
authors.initials: RL
authors.lastname: Rasmusson
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: jsaeij@mit.edu.
authors.forename: Jeroen P J
authors.initials: JP
authors.lastname: Saeij
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D017353:Gene Deletion; D005816:Genetic Complementation Test; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D014122:Toxoplasma / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D014124:Toxoplasmosis, Animal / Q000469:parasitology / Q000473:pathology; D014617:Vacuoles / Q000469:parasitology*; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*; D014981:Xenopus
chemical_list: D000953:Antigens, Protozoan; D026901:Membrane Transport Proteins; D037521:Virulence Factors