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Rapid kinetics of lipid second messengers controlled by a cGMP signalling network coordinates apical complex functions in Toxoplasma tachyzoites

Rapid kinetics of lipid second messengers controlled by a cGMP signalling network coordinates apical complex functions in Toxoplasma tachyzoites
Rapid kinetics of lipid second messengers controlled by a cGMP signalling network coordinates apical complex functions in Toxoplasma tachyzoites
Host cell invasion and subsequent egress by Toxoplasma parasites is regulated by a network of cGMP, cAMP, and calcium signalling proteins. Such eukaryotic signalling networks typically involve lipid second messengers including phosphatidylinositol phosphates (PIPs), diacylglycerol (DAG) and phosphatidic acid (PA). However, the lipid signalling network in Toxoplasma is poorly defined. Here we present lipidomic analysis of a mutant of central flippase/guanylate cyclase TgGC in Toxoplasma, which we show has disrupted turnover of signalling lipids impacting phospholipid metabolism and membrane stability. The turnover of signalling lipids is extremely rapid in extracellular parasites and we track changes in PA and DAG to within 5 seconds, which are variably defective upon disruption of TgGC and other signalling proteins. We then identify the position of each protein in the signal chain relative to the central cGMP signalling protein TgGC and map the lipid signal network coordinating conoid extrusion and microneme secretion for egress and invasion.
Katris, Nicholas J.
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Yamaryo-Botte, Yoshiki
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Janouškovec, Jan
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Shunmugam, Serena
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Arnold, Christophe-Sebastien
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Yang, Annie S. P.
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Vardakis, Alexandros
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Stewart, Rebecca J.
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Sauerwein, Robert
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McFadden, Geoffrey I.
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Tonkin, Christopher J.
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Cesbron-Delauw, Marie-France
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Waller, Ross F.
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Botte, Cyrille Y.
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Katris, Nicholas J.
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Yamaryo-Botte, Yoshiki
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Janouškovec, Jan
fbaa4a5d-872e-465b-b2c3-bb35df455cc6
Shunmugam, Serena
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Arnold, Christophe-Sebastien
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Yang, Annie S. P.
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Vardakis, Alexandros
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Stewart, Rebecca J.
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Sauerwein, Robert
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McFadden, Geoffrey I.
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Tonkin, Christopher J.
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Cesbron-Delauw, Marie-France
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Waller, Ross F.
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Botte, Cyrille Y.
a66f9207-c439-41e8-8589-d19cb61dfc85

[Unknown type: UNSPECIFIED]

Record type: UNSPECIFIED

Abstract

Host cell invasion and subsequent egress by Toxoplasma parasites is regulated by a network of cGMP, cAMP, and calcium signalling proteins. Such eukaryotic signalling networks typically involve lipid second messengers including phosphatidylinositol phosphates (PIPs), diacylglycerol (DAG) and phosphatidic acid (PA). However, the lipid signalling network in Toxoplasma is poorly defined. Here we present lipidomic analysis of a mutant of central flippase/guanylate cyclase TgGC in Toxoplasma, which we show has disrupted turnover of signalling lipids impacting phospholipid metabolism and membrane stability. The turnover of signalling lipids is extremely rapid in extracellular parasites and we track changes in PA and DAG to within 5 seconds, which are variably defective upon disruption of TgGC and other signalling proteins. We then identify the position of each protein in the signal chain relative to the central cGMP signalling protein TgGC and map the lipid signal network coordinating conoid extrusion and microneme secretion for egress and invasion.

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In preparation date: 20 June 2020
Additional Information: The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.

Identifiers

Local EPrints ID: 468048
URI: http://eprints.soton.ac.uk/id/eprint/468048
PURE UUID: f5f18c41-5cc3-4c4f-af64-4139503c3d7c
ORCID for Jan Janouškovec: ORCID iD orcid.org/0000-0001-6547-749X

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Date deposited: 28 Jul 2022 18:49
Last modified: 17 Mar 2024 04:11

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Contributors

Author: Nicholas J. Katris
Author: Yoshiki Yamaryo-Botte
Author: Jan Janouškovec ORCID iD
Author: Serena Shunmugam
Author: Christophe-Sebastien Arnold
Author: Annie S. P. Yang
Author: Alexandros Vardakis
Author: Rebecca J. Stewart
Author: Robert Sauerwein
Author: Geoffrey I. McFadden
Author: Christopher J. Tonkin
Author: Marie-France Cesbron-Delauw
Author: Ross F. Waller
Author: Cyrille Y. Botte

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