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2021-01-21Zeitschriftenartikel DOI: 10.18452/23508
Aminoglycerophospholipid flipping and P4-ATPases in Toxoplasma gondii
dc.contributor.authorChen, Kai
dc.contributor.authorGünay-Esiyok, Özlem
dc.contributor.authorKlingeberg, Melissa
dc.contributor.authorMarquardt, Stephan
dc.contributor.authorGünther Pomorski, Thomas
dc.contributor.authorGupta, Nishith
dc.date.accessioned2021-10-12T10:43:52Z
dc.date.available2021-10-12T10:43:52Z
dc.date.issued2021-01-21none
dc.identifier.other10.1016/j.jbc.2021.100315
dc.identifier.urihttp://edoc.hu-berlin.de/18452/24159
dc.description.abstractLipid flipping in the membrane bilayers is a widespread eukaryotic phenomenon that is catalyzed by assorted P4-ATPases. Its occurrence, mechanism, and importance in apicomplexan parasites have remained elusive, however. Here we show that Toxoplasma gondii, an obligate intracellular parasite with high clinical relevance, can salvage phosphatidylserine (PtdSer) and phosphatidylethanolamine (PtdEtn) but not phosphatidylcholine (PtdCho) probes from its milieu. Consistently, the drug analogs of PtdCho are broadly ineffective in the parasite culture. NBD-PtdSer imported to the parasite interior is decarboxylated to NBD-PtdEtn, while the latter is not methylated to yield PtdCho, which confirms the expression of PtdSer decarboxylase but a lack of PtdEtn methyltransferase activity and suggests a role of exogenous lipids in membrane biogenesis of T. gondii. Flow cytometric quantitation of NBD-probes endorsed the selectivity of phospholipid transport and revealed a dependence of the process on energy and protein. Accordingly, our further work identified five P4-ATPases (TgP4-ATPase1-5), all of which harbor the signature residues and motifs required for phospholipid flipping. Of the four proteins expressed during the lytic cycle, TgP4-ATPase1 is present in the apical plasmalemma; TgP4-ATPase3 resides in the Golgi network along with its noncatalytic partner Ligand Effector Module 3 (TgLem3), whereas TgP4-ATPase2 and TgP4-ATPase5 localize in the plasmalemma as well as endo/cytomembranes. Last but not least, auxin-induced degradation of TgP4-ATPase1-3 impaired the parasite growth in human host cells, disclosing their crucial roles during acute infection. In conclusion, we show selective translocation of PtdEtn and PtdSer at the parasite surface and provide the underlying mechanistic and physiological insights in a model eukaryotic pathogen.eng
dc.language.isoengnone
dc.publisherHumboldt-Universität zu Berlin
dc.rights(CC BY 4.0) Attribution 4.0 Internationalger
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectNBD-lipideng
dc.subjectphosphatidylserineeng
dc.subjectphosphatidylethanolamineeng
dc.subjectP4-ATPaseeng
dc.subjectLem3/Cdc50eng
dc.subject.ddc570 Biologienone
dc.titleAminoglycerophospholipid flipping and P4-ATPases in Toxoplasma gondiinone
dc.typearticle
dc.identifier.urnurn:nbn:de:kobv:11-110-18452/24159-1
dc.identifier.doihttp://dx.doi.org/10.18452/23508
dc.type.versionpublishedVersionnone
local.edoc.container-titleThe journal of biological chemistrynone
local.edoc.pages17none
local.edoc.anmerkungThis article was supported by the German Research Foundation (DFG) and the Open Access Publication Fund of Humboldt-Universität zu Berlin.none
local.edoc.type-nameZeitschriftenartikel
local.edoc.institutionLebenswissenschaftliche Fakultätnone
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-publisher-nameASBMB Publicationsnone
local.edoc.container-publisher-placeBethesda, Md.none
local.edoc.container-volume296none
dc.description.versionPeer Reviewednone
local.edoc.container-articlenumber100315none
dc.identifier.eissn1083-351X

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