TY - JOUR
T1 - EXP2 is a nutrient-permeable channel in the vacuolar membrane of Plasmodium and is essential for protein export via PTEX
AU - Garten, Matthias
AU - Nasamu, Armiyaw S.
AU - Niles, Jacquin C.
AU - Zimmerberg, Joshua
AU - Goldberg, Daniel E.
AU - Beck, Josh R.
N1 - Funding Information:
This work was supported by NIH grants HL133453 to J.R.B. and AI47798 to D.E.G. and by the Division of Intramural Research of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. We thank S. Glushakova for creating and applying the parasite liberation technique, for performing the IMF experiment and for many helpful conversations throughout the course of this project. We thank J. McBride, D. Cavanagh and EMRR for the EXP2 antibody, D. Taylor for HRP2 antibody, C. Braun-Breton for SBP1 antibody, W. Beatty for assistance with electron microscopy, P. Gurnev for the buffer conductivity measurement, P. S. Blank for helpful suggestions for the statistical analysis of the patch-clamp data and B. Vaupel for technical assistance.
Publisher Copyright:
© 2018, The Author(s).
PY - 2018/10/1
Y1 - 2018/10/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85052861980&partnerID=8YFLogxK
U2 - 10.1038/s41564-018-0222-7
DO - 10.1038/s41564-018-0222-7
M3 - Letter
C2 - 30150733
AN - SCOPUS:85052861980
VL - 3
SP - 1090
EP - 1098
JO - Nature Microbiology
JF - Nature Microbiology
SN - 2058-5276
IS - 10
ER -