EXP2 is a nutrient-permeable channel in the vacuolar membrane of Plasmodium and is essential for protein export via PTEX

Nature Microbiology
Matthias GartenJosh R Beck

Abstract

Intraerythrocytic malaria parasites reside within a parasitophorous vacuolar membrane (PVM) generated during host cell invasion1. Erythrocyte remodelling and parasite metabolism require the export of effector proteins and transport of small molecules across this barrier between the parasite surface and host cell cytosol2,3. Protein export across the PVM is accomplished by the Plasmodium translocon of exported proteins (PTEX) consisting of three core proteins, the AAA+ ATPase HSP101 and two additional proteins known as PTEX150 and EXP24. Inactivation of HSP101 and PTEX150 arrests protein export across the PVM5,6, but the contribution of EXP2 to parasite biology is not well understood7. A nutrient permeable channel in the PVM has also been characterized electrophysiologically, but its molecular identity is unknown8,9. Here, using regulated gene expression, mutagenesis and cell-attached patch-clamp measurements, we show that EXP2, the putative membrane-spanning channel of PTEX4,10-14, serves dual roles as a protein-conducting channel in the context of PTEX and as a channel able to facilitate nutrient passage across the PVM independent of HSP101. Our data suggest a dual functionality for a channel operating in its endogenous context.

References

Jan 18, 1994·Proceedings of the National Academy of Sciences of the United States of America·J C SchwabK A Joiner
Mar 4, 1997·Proceedings of the National Academy of Sciences of the United States of America·S A Desai, R L Rosenberg
Feb 12, 1998·Biochimica Et Biophysica Acta·V LevadnyM Belaya
Nov 23, 2000·Molecular and Biochemical Parasitology·T BlisnickC Braun Breton
Jan 8, 2004·The Journal of Cell Biology·Michael KlembaDaniel E Goldberg
Sep 20, 2005·Current Biology : CB·Svetlana GlushakovaJoshua Zimmerberg
Jun 19, 2009·Nature·Tania F de Koning-WardBrendan S Crabb
Feb 10, 2010·Molecular Microbiology·Thomas D OttoManuel Llinás
Aug 14, 2010·Nature Reviews. Microbiology·Daniel E Goldberg, Alan F Cowman
Jan 22, 2011·Molecular and Biochemical Parasitology·Suresh M GanesanAkhil B Vaidya
Nov 2, 2011·Proceedings of the National Academy of Sciences of the United States of America·Sophie H AdjalleyDavid A Fidock
Mar 22, 2012·Cellular Microbiology·Sanjay A Desai
Jul 3, 2013·Annual Review of Microbiology·Justin A Boddey, Alan F Cowman
Apr 2, 2014·The Journal of Infectious Diseases·Svetlana GlushakovaJoshua Zimmerberg
Jul 22, 2014·Nature·Brendan ElsworthTania F de Koning-Ward
Jul 25, 2014·Nature Communications·Ann M GuggisbergAudrey R Odom
Jan 22, 2015·Journal of Biological Methods·Arthur D EdelsteinNico Stuurman
Sep 3, 2016·FEMS Microbiology Reviews·Emma S Sherling, Christiaan van Ooij
Nov 21, 2016·Biochemical and Biophysical Research Communications·Kazuaki HakamadaMasafumi Yohda
Dec 23, 2016·Proceedings of the National Academy of Sciences of the United States of America·Matthias GartenGilman E S Toombes
Jan 10, 2017·Cellular Microbiology·Natalie J SpillmanDaniel E Goldberg

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Citations

Dec 6, 2018·PloS One·Nonlawat BoonyalaiMichael J Blackman
Jan 19, 2019·Cellular Microbiology·Kathryn M MatthewsTania F de Koning-Ward
Mar 20, 2019·Scientific Reports·Jan-Gero SchloetelMichał Pasternak
Nov 27, 2019·The Journal of Biological Chemistry·Aarti KrishnanDominique Soldati-Favre
Jan 29, 2020·Cellular Microbiology·Timothy NesselJosh R Beck
May 11, 2020·Cellular Microbiology·Anat FlorentinVasant Muralidharan
May 6, 2020·The Journal of Biological Chemistry·Armiyaw S NasamuDaniel E Goldberg
Jul 19, 2020·Annual Review of Microbiology·Yifan WangJeroen P J Saeij
Nov 9, 2019·Biological Reviews of the Cambridge Philosophical Society·Rowena E Martin
Jan 26, 2020·Nature Reviews. Microbiology·Joachim M MatzMichael J Blackman
Sep 5, 2018·Nature Reviews. Microbiology·Ashley York
Oct 2, 2019·Frontiers in Cellular and Infection Microbiology·Tatiana Paredes-SantosJeroen P Saeij
Sep 6, 2018·Nature·Tania F de Koning-Ward
Aug 26, 2019·Current Opinion in Microbiology·Suchita RastogiJohn C Boothroyd
Dec 24, 2019·Trends in Parasitology·Daniel E Goldberg, Joshua Zimmerberg
Apr 25, 2020·Cell Chemical Biology·Dora PosfaiEmily R Derbyshire
Apr 2, 2021·PLoS Pathogens·Josh R Beck, Chi-Min Ho
Apr 13, 2021·Frontiers in Cell and Developmental Biology·Natalie A CounihanTania F de Koning-Ward
Apr 23, 2021·PLoS Pathogens·Heather M KudybaVasant Muralidharan
May 15, 2021·Trends in Parasitology·Thorey K JonsdottirPaul R Gilson
Jun 23, 2021·Nature Communications·Felix EversTaco W A Kooij
Jul 2, 2021·Frontiers in Cellular and Infection Microbiology·Kayla SylvesterEmily R Derbyshire
Aug 11, 2021·Current Opinion in Microbiology·Matthias Garten, Josh R Beck
Feb 19, 2020·ACS Infectious Diseases·Alexander J PolinoDaniel E Goldberg
Aug 17, 2021·Frontiers in Cellular and Infection Microbiology·Monrat Chulanetra, Wanpen Chaicumpa

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Methods Mentioned

BETA
transmission electron microscopy
electron microscopy
immunoprecipitation
co-immunoprecipitation
PCR
flow cytometry
electrophoresis

Software Mentioned

Prism
AxioVision
Excel
Micro Manager
ClampFit10
MATLAB
Prism Graphpad
AMT Image Capture Engine
R
R core Team

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