The Obligate Intracellular Parasite Toxoplasma gondii Secretes a Soluble Phosphatidylserine Decarboxylase

Gupta, Nishith; Hartmann, Anne; Lucius, Richard; Voelker, Dennis R.

doi:10.1074/jbc.m112.373639

Cited by 33 publications

(45 citation statements)

References 34 publications

(48 reference statements)

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“…In contrast, TgPSD1pv, regulated by its endogenous promoter, was localized in the parasitophorous vacuole (Fig. 2B) (13). These data reveal two phylogenetically distinct PSD enzymes in T. gondii, one of which is secreted into the parasitophorous vacuole (TgPSD1pv), and a second one that is expressed in the parasite mitochondrion (TgPSD1mt).…”

Section: Volume 289 • Number 10 • March 7 2014mentioning

confidence: 77%

“…Is a Type I PtdSer Decarboxylase Localized in the Parasite Mitochondrion-Our earlier studies characterized a partially soluble PSD enzyme in T. gondii, which is secreted into the parasitophorous vacuole (TgPSD1pv) via dense granules (13). This work and subsequent database mining also indicated the presence of a second PSD gene in the parasite (ToxoDB; TGGT1_225550).…”

Section: Tgpsd1mtmentioning

confidence: 93%

“…Quite notably, T. gondii tachyzoites display a much higher (10-fold) PSD activity when compared with yeast and mammalian cells (4). We have shown that the PSD activity in T. gondii comprises membrane-bound and soluble fractions (13). The PSD attributed to the soluble activity is secreted/excreted into the parasitophorous vacuole (TgPSD1pv) via dense granules (13), whereas the other PSD has, so far, remained elusive.…”

mentioning

confidence: 98%

“…We have shown that the PSD activity in T. gondii comprises membrane-bound and soluble fractions (13). The PSD attributed to the soluble activity is secreted/excreted into the parasitophorous vacuole (TgPSD1pv) via dense granules (13), whereas the other PSD has, so far, remained elusive. This study aimed to (a) characterize the membrane-associated PSD for its activity and subcellular location, (b) determine its relative importance for PtdEtn synthesis, and (c) examine the cooperativity of distinct routes of PtdEtn synthesis for membrane biogenesis, survival, and growth of T. gondii, if any.…”

mentioning

confidence: 99%

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Phosphatidylethanolamine Synthesis in the Parasite Mitochondrion Is Required for Efficient Growth but Dispensable for Survival of Toxoplasma gondii

Hartmann

Hellmund

Lucius

et al. 2014

Journal of Biological Chemistry

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Background: Toxoplasma gondii is a common intracellular parasite of diverse host cells. Results:The parasite can produce phosphatidylethanolamine in its mitochondrion, endoplasmic reticulum, and parasitophorous vacuole, which together allow versatile lipid biogenesis. Conclusion: Multiple routes of lipid synthesis ensure parasite survival in discrete nutrient milieus. Significance: T. gondii offers an instructive model to study membrane biology of parasitic protists.

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Section: Volume 289 • Number 10 • March 7 2014mentioning

confidence: 77%

Section: Tgpsd1mtmentioning

confidence: 93%

mentioning

confidence: 98%

mentioning

confidence: 99%

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Phosphatidylethanolamine Synthesis in the Parasite Mitochondrion Is Required for Efficient Growth but Dispensable for Survival of Toxoplasma gondii

Hartmann

Hellmund

Lucius

et al. 2014

Journal of Biological Chemistry

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“…The distribution of TgLCAT to the IVN suggests a role for this enzyme in the remodeling of the IVN membranes by producing lysophosphatidylcholine that can shape membranes and change their curvature. A precedent for potential activity of lipid-modifying enzymes in the PV is illustrated by a phosphatidylserine decarboxylase, TgPSD, that is secreted by the parasite into the PV lumen (66). Phosphatidylethanolamine produced by TgPSD is a potent inducer of changes in protein conformation, which influences the lateral movement and activity of membrane-bound proteins (67).…”

Section: Discussionmentioning

confidence: 99%

A Lipolytic Lecithin:Cholesterol Acyltransferase Secreted by Toxoplasma Facilitates Parasite Replication and Egress

Pszenny

Ehrenman

Romano

et al. 2016

Journal of Biological Chemistry

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The protozoan parasite Toxoplasma gondii develops within a parasitophorous vacuole (PV) in mammalian cells, where it scavenges cholesterol. When cholesterol is present in excess in its environment, the parasite expulses this lipid into the PV or esterifies it for storage in lipid bodies. Here, we characterized a unique T. gondii homologue of mammalian lecithin:cholesterol acyltransferase (LCAT), a key enzyme that produces cholesteryl esters via transfer of acyl groups from phospholipids to the 3-OH of free cholesterol, leading to the removal of excess cholesterol from tissues. TgLCAT contains a motif characteristic of serine lipases "AHSLG" and the catalytic triad consisting of serine, aspartate, and histidine (SDH) from LCAT enzymes. TgL-CAT is secreted by the parasite, but unlike other LCAT enzymes it is cleaved into two proteolytic fragments that share the residues of the catalytic triad and need to be reassembled to reconstitute enzymatic activity. TgLCAT uses phosphatidylcholine as substrate to form lysophosphatidylcholine that has the potential to disrupt membranes. The released fatty acid is transferred to cholesterol, but with a lower transesterification activity than mammalian LCAT. TgLCAT is stored in a subpopulation of dense granule secretory organelles, and following secretion, it localizes to the PV and parasite plasma membrane. LCAT-null parasites have impaired growth in vitro, reduced virulence in animals, and exhibit delays in egress from host cells. Parasites overexpressing LCAT show increased virulence and faster egress. These observations demonstrate that TgLCAT influences the outcome of an infection, presumably by facilitating replication and egress depending on the developmental stage of the parasite.The phospholipase A 2 (PLA 2 ) 2 family of serine lipases comprises more than 30 enzymes in mammals. The PLA 2 members hydrolyze the sn-2 ester of phospholipids, yielding lysophospholipid and releasing a fatty acid (1). Approximately one-third of the PLA 2 family members are secreted from cells and display various localizations post-secretion, reflecting their specialized biological functions (2). Among the secretory PLA 2 , lecithin: cholesterol acyltransferase (LCAT; EC 2.3.1.43) is characterized by dual activity, PLA 2 and acyltransferase. In mammals, this enzyme catalyzes the transacylation of the sn-2 fatty acid liberated from various phospholipids (e.g. phosphatidylcholine or phosphatidylethanolamine) to the 3-␤-hydroxyl group on the A-ring of cholesterol, thereby forming cholesteryl esters (3-5). The primary sequence of LCAT is well conserved between mammalian species (6). A structural model for LCAT predicts the conformation of a catalytic triad formed by SerAsp-His residues involved in the phospholipase reaction (7). Mammalian LCATs are primarily expressed in the liver and secreted to the plasma where they circulate in association with HDL (8). These enzymes are components of the reverse cholesterol transport pathway by which cholesterol from peripheral cells is delivered to the liver f...

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Unique asymmetric distribution of phosphatidylserine and phosphatidylethanolamine in Toxoplasma gondii revealed by nanoscale analysis

Konishi

Fukuda

Kuriyama

et al. 2023

Histochem Cell Biol

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The Obligate Intracellular Parasite Toxoplasma gondii Secretes a Soluble Phosphatidylserine Decarboxylase

Cited by 33 publications

References 34 publications

Phosphatidylethanolamine Synthesis in the Parasite Mitochondrion Is Required for Efficient Growth but Dispensable for Survival of Toxoplasma gondii

Phosphatidylethanolamine Synthesis in the Parasite Mitochondrion Is Required for Efficient Growth but Dispensable for Survival of Toxoplasma gondii

A Lipolytic Lecithin:Cholesterol Acyltransferase Secreted by Toxoplasma Facilitates Parasite Replication and Egress

Unique asymmetric distribution of phosphatidylserine and phosphatidylethanolamine in Toxoplasma gondii revealed by nanoscale analysis

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