Gold Daniel A, Kaplan Aaron D, Lis Agnieszka, Bett Glenna C L, Rosowski Emily E, Cirelli Kimberly M, Bougdour Alexandre, Sidik Saima M, Beck Josh R, Lourido Sebastian, Egea Pascal F, Bradley Peter J, Hakimi Mohamed-Ali, Rasmusson Randall L, Saeij Jeroen P J
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
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.
Cell Host Microbe. 2015 May 13;17(5):642-52. doi: 10.1016/j.chom.2015.04.003.
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.
刚地弓形虫是顶复门的一种原生动物病原体，它寄生于细胞内的寄生泡（PV）中，该寄生泡通过未知机制对小分子具有选择性通透性。我们已鉴定出GRA17是一种刚地弓形虫分泌蛋白，定位于寄生泡膜（PVM），并介导小分子跨PVM的被动转运。GRA17与推定的疟原虫转运蛋白EXP2相关，并且在寄生于PV的顶复门中保守。缺乏GRA17的寄生虫的PV具有异常形态，对小分子的通透性降低，且结构不稳定。缺乏GRA17的寄生虫增殖缓慢，在小鼠中无致病性。通过与疟原虫EXP2互补可挽救这些缺乏GRA17的表型。GRA17与相关蛋白GRA23协同发挥作用。GRA17或GRA23的外源表达以与大的非选择性孔一致的方式改变非洲爪蟾卵母细胞的膜电导特性。因此，GRA17和GRA23为PVM通透性和营养物质获取提供了分子基础。
