A Toxoplasma gondii protein with homology to intracellular type Na+/H+ exchangers is important for osmoregulation and invasion

Maria E. Francia, Sarah Wicher, Douglas A. Pace, Jack Sullivan, Silvia N J Moreno, Gustavo Arrizabalaga

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The obligate intracellular parasite Toxoplasma gondii is exposed to a variety of physiological conditions while propagating in an infected organism. The mechanisms by which Toxoplasma overcomes these dramatic changes in its environment are not known. In yeast and plants, ion detoxification and osmotic regulation are controlled by vacuolar compartments. A novel compartment named the plant-like vacuole or vacuolar compartment (PLV/VAC) has recently been described in T.gondii, which could potentially protect extracellular tachyzoites against salt and other ionic stresses. Here, we report the molecular characterization of the vacuolar type Na+/H+ exchanger in T. gondii, TgNHE3, and its co-localization with the PLV/VAC proton-pyrophosphatase (TgVP1). We have created a TgNHE3 knockout strain, which is more sensitive to hyperosmotic shock and toxic levels of sodium, possesses a higher intracellular Ca2+ concentration [Ca2+]i, and exhibits a reduced host invasion efficiency. The defect in invasion correlates with a measurable reduction in the secretion of the adhesin TgMIC2. Overall, our results suggest that the PLV/VAC has functions analogous to those of the vacuolar compartments of plants and yeasts, providing the parasite with a mechanism to resist ionic fluctuations and, potentially, regulate protein trafficking.

Original languageEnglish (US)
Pages (from-to)1382-1396
Number of pages15
JournalExperimental Cell Research
Volume317
Issue number10
DOIs
StatePublished - Jun 10 2011
Externally publishedYes

Fingerprint

Osmoregulation
Sodium-Hydrogen Antiporter
Toxoplasma
Vacuoles
Proteins
Parasites
Yeasts
Pyrophosphatases
Protein Transport
Septic Shock
Protons
Salts
Sodium
Ions

Keywords

  • Invasion
  • NHE
  • Processing
  • Secretion
  • Toxoplasma gondii
  • Vacuole
  • VP1

ASJC Scopus subject areas

  • Cell Biology

Cite this

A Toxoplasma gondii protein with homology to intracellular type Na+/H+ exchangers is important for osmoregulation and invasion. / Francia, Maria E.; Wicher, Sarah; Pace, Douglas A.; Sullivan, Jack; Moreno, Silvia N J; Arrizabalaga, Gustavo.

In: Experimental Cell Research, Vol. 317, No. 10, 10.06.2011, p. 1382-1396.

Research output: Contribution to journalArticle

Francia, Maria E. ; Wicher, Sarah ; Pace, Douglas A. ; Sullivan, Jack ; Moreno, Silvia N J ; Arrizabalaga, Gustavo. / A Toxoplasma gondii protein with homology to intracellular type Na+/H+ exchangers is important for osmoregulation and invasion. In: Experimental Cell Research. 2011 ; Vol. 317, No. 10. pp. 1382-1396.
@article{d4a4805cd295404a9132884e04107a94,
title = "A Toxoplasma gondii protein with homology to intracellular type Na+/H+ exchangers is important for osmoregulation and invasion",
abstract = "The obligate intracellular parasite Toxoplasma gondii is exposed to a variety of physiological conditions while propagating in an infected organism. The mechanisms by which Toxoplasma overcomes these dramatic changes in its environment are not known. In yeast and plants, ion detoxification and osmotic regulation are controlled by vacuolar compartments. A novel compartment named the plant-like vacuole or vacuolar compartment (PLV/VAC) has recently been described in T.gondii, which could potentially protect extracellular tachyzoites against salt and other ionic stresses. Here, we report the molecular characterization of the vacuolar type Na+/H+ exchanger in T. gondii, TgNHE3, and its co-localization with the PLV/VAC proton-pyrophosphatase (TgVP1). We have created a TgNHE3 knockout strain, which is more sensitive to hyperosmotic shock and toxic levels of sodium, possesses a higher intracellular Ca2+ concentration [Ca2+]i, and exhibits a reduced host invasion efficiency. The defect in invasion correlates with a measurable reduction in the secretion of the adhesin TgMIC2. Overall, our results suggest that the PLV/VAC has functions analogous to those of the vacuolar compartments of plants and yeasts, providing the parasite with a mechanism to resist ionic fluctuations and, potentially, regulate protein trafficking.",
keywords = "Invasion, NHE, Processing, Secretion, Toxoplasma gondii, Vacuole, VP1",
author = "Francia, {Maria E.} and Sarah Wicher and Pace, {Douglas A.} and Jack Sullivan and Moreno, {Silvia N J} and Gustavo Arrizabalaga",
year = "2011",
month = "6",
day = "10",
doi = "10.1016/j.yexcr.2011.03.020",
language = "English (US)",
volume = "317",
pages = "1382--1396",
journal = "Experimental Cell Research",
issn = "0014-4827",
publisher = "Academic Press Inc.",
number = "10",

}

TY - JOUR

T1 - A Toxoplasma gondii protein with homology to intracellular type Na+/H+ exchangers is important for osmoregulation and invasion

AU - Francia, Maria E.

AU - Wicher, Sarah

AU - Pace, Douglas A.

AU - Sullivan, Jack

AU - Moreno, Silvia N J

AU - Arrizabalaga, Gustavo

PY - 2011/6/10

Y1 - 2011/6/10

N2 - The obligate intracellular parasite Toxoplasma gondii is exposed to a variety of physiological conditions while propagating in an infected organism. The mechanisms by which Toxoplasma overcomes these dramatic changes in its environment are not known. In yeast and plants, ion detoxification and osmotic regulation are controlled by vacuolar compartments. A novel compartment named the plant-like vacuole or vacuolar compartment (PLV/VAC) has recently been described in T.gondii, which could potentially protect extracellular tachyzoites against salt and other ionic stresses. Here, we report the molecular characterization of the vacuolar type Na+/H+ exchanger in T. gondii, TgNHE3, and its co-localization with the PLV/VAC proton-pyrophosphatase (TgVP1). We have created a TgNHE3 knockout strain, which is more sensitive to hyperosmotic shock and toxic levels of sodium, possesses a higher intracellular Ca2+ concentration [Ca2+]i, and exhibits a reduced host invasion efficiency. The defect in invasion correlates with a measurable reduction in the secretion of the adhesin TgMIC2. Overall, our results suggest that the PLV/VAC has functions analogous to those of the vacuolar compartments of plants and yeasts, providing the parasite with a mechanism to resist ionic fluctuations and, potentially, regulate protein trafficking.

AB - The obligate intracellular parasite Toxoplasma gondii is exposed to a variety of physiological conditions while propagating in an infected organism. The mechanisms by which Toxoplasma overcomes these dramatic changes in its environment are not known. In yeast and plants, ion detoxification and osmotic regulation are controlled by vacuolar compartments. A novel compartment named the plant-like vacuole or vacuolar compartment (PLV/VAC) has recently been described in T.gondii, which could potentially protect extracellular tachyzoites against salt and other ionic stresses. Here, we report the molecular characterization of the vacuolar type Na+/H+ exchanger in T. gondii, TgNHE3, and its co-localization with the PLV/VAC proton-pyrophosphatase (TgVP1). We have created a TgNHE3 knockout strain, which is more sensitive to hyperosmotic shock and toxic levels of sodium, possesses a higher intracellular Ca2+ concentration [Ca2+]i, and exhibits a reduced host invasion efficiency. The defect in invasion correlates with a measurable reduction in the secretion of the adhesin TgMIC2. Overall, our results suggest that the PLV/VAC has functions analogous to those of the vacuolar compartments of plants and yeasts, providing the parasite with a mechanism to resist ionic fluctuations and, potentially, regulate protein trafficking.

KW - Invasion

KW - NHE

KW - Processing

KW - Secretion

KW - Toxoplasma gondii

KW - Vacuole

KW - VP1

UR - http://www.scopus.com/inward/record.url?scp=79955965936&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79955965936&partnerID=8YFLogxK

U2 - 10.1016/j.yexcr.2011.03.020

DO - 10.1016/j.yexcr.2011.03.020

M3 - Article

VL - 317

SP - 1382

EP - 1396

JO - Experimental Cell Research

JF - Experimental Cell Research

SN - 0014-4827

IS - 10

ER -