The Toxoplasma Dense Granule Proteins GRA17 and GRA23 Mediate the Movement of Small Molecules between the Host and the Parasitophorous Vacuole

被引：185

作者：

Gold, Daniel A. ^{[1
]}

Kaplan, Aaron D. ^{[2
,3
]}

Lis, Agnieszka ^{[2
,3
]}

Bett, Glenna C. L. ^{[2
,3
,4
]}

Rosowski, Emily E. ^{[1
]}

Cirelli, Kimberly M. ^{[1
]}

Bougdour, Alexandre ^{[5
,6
]}

Sidik, Saima M. ^{[7
]}

Beck, Josh R. ^{[8
]}

Lourido, Sebastian ^{[6
]}

Egea, Pascal F. ^{[9
]}

Bradley, Peter J. ^{[8
]}

Hakimi, Mohamed-Ali ^{[5
,6
]}

Rasmusson, Randall L. ^{[2
,3
]}

Saeij, Jeroen P. J. ^{[1
]}

机构：

[1] MIT, Dept Biol, Cambridge, MA 02139 USA

[2] SUNY Buffalo, Physiol & Biophys, Buffalo, NY 14214 USA

[3] SUNY Buffalo, Sch Med & Biomed Sci, Ctr Cellular & Syst Electrophysiol, Buffalo, NY 14214 USA

[4] SUNY Buffalo, Sch Med & Biomed Sci, Dept Obstet & Gynocol, Buffalo, NY 14214 USA

[5] CNRS, UMR5163, LAPM, F-38041 Grenoble, France

[6] Univ Grenoble 1, F-38000 Grenoble, France

[7] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA

[8] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA

[9] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA

来源：

CELL HOST & MICROBE | 2015年 / 17卷 / 05期

关键词：

MALARIA PARASITES; GONDII; EXPORT; APICOMPLEXA; MEMBRANE; SUBVERSION; EXPRESSION; EFFECTORS; NETWORK; TARGETS;

D O I：

10.1016/j.chom.2015.04.003

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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 PVresiding 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.

引用

页码：642 / 652

页数：11

共 32 条

[1] PTEX component HSP101 mediates export of diverse malaria effectors into host erythrocytes [J].