ATP11C Facilitates Phospholipid Translocation across the Plasma Membrane of All Leukocytes

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dc.authoridJing, Weidong/0000-0002-6747-6076
dc.authoridEnders, Anselm/0000-0001-5933-6463
dc.authoridYabas, Mehmet/0000-0002-3462-5389
dc.authoridBroer, Stefan/0000-0002-8040-1634
dc.authoridShafik, Sarah/0000-0001-6503-3565
dc.authorwosidJing, Weidong/D-7145-2019
dc.authorwosidShafik, Sarah/AAW-5156-2020
dc.authorwosidEnders, Anselm/B-1165-2011
dc.authorwosidYabas, Mehmet/D-9513-2012
dc.authorwosidBroer, Stefan/A-1286-2008
dc.contributor.authorYabas, Mehmet
dc.contributor.authorJing, Weidong
dc.contributor.authorShafik, Sarah
dc.contributor.authorBroeer, Stefan
dc.contributor.authorEnders, Anselm
dc.date.accessioned2024-06-12T11:19:44Z
dc.date.available2024-06-12T11:19:44Z
dc.date.issued2016
dc.departmentTrakya Üniversitesien_US
dc.description.abstractOrganization of the plasma membrane into specialized substructures in different blood lineages facilitates important biological functions including proper localization of receptors at the plasma membrane as well as the initiation of crucial intracellular signaling cascades. The eukaryotic plasma membrane is a lipid bilayer that consists of asymmetrically distributed phospholipids. This asymmetry is actively maintained by membrane-embedded lipid transporters, but there is only limited data available about the molecular identity of the predominantly active transporters and their substrate specificity in different leukocyte subsets. We demonstrate here that the P4-type ATPase ATP11C mediates significant flippase activity in all murine leukocyte subsets. Loss of ATP11C resulted in a defective internalization of phosphatidylserine (PS) and phosphatidylethanolamine (PE) in comparison to control cells. The diminished flippase activity caused increased PS exposure on 7-aminoactinomycin D- (7-AAD(-)) viable pro-B cells freshly isolated from the bone marrow of ATP11C-deficient mice, which was corrected upon a 2-hour resting period in vitro. Despite the impaired flippase activity in all immune cell subsets, the only other blood cell type with an accumulation of PS on the surface were viable 7-AAD(-) developing T cells but this did not result in any discernable effect on their development in the thymus. These findings show that all leukocyte lineages exhibit flippase activity, and identify ATP11C as an aminophospholipid translocase in immune cells.en_US
dc.description.sponsorshipNational Health and Medical Research Council [GNT1061288]; Ministry of National Education, Republic of Turkey; National Health and Medical Research Council Career Development Fellowship [GNT1035858]; Ramaciotti Foundationen_US
dc.description.sponsorshipThis work was supported by National Health and Medical Research Council Grant GNT1061288. MY was supported by a postgraduate award from the Ministry of National Education, Republic of Turkey, and AE was supported by a National Health and Medical Research Council Career Development Fellowship GNT1035858 and by the Ramaciotti Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en_US
dc.identifier.doi10.1371/journal.pone.0146774
dc.identifier.issn1932-6203
dc.identifier.issue1en_US
dc.identifier.pmid26799398en_US
dc.identifier.scopus2-s2.0-84958214585en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1371/journal.pone.0146774
dc.identifier.urihttps://hdl.handle.net/20.500.14551/25313
dc.identifier.volume11en_US
dc.identifier.wosWOS:000368655300034en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherPublic Library Scienceen_US
dc.relation.ispartofPlos Oneen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectP-Type Atpasesen_US
dc.subjectAnnexin-V Bindsen_US
dc.subjectB-Cellsen_US
dc.subjectPhosphatidylserineen_US
dc.subjectFlippasesen_US
dc.subjectExpressionen_US
dc.subjectLymphocytesen_US
dc.subjectDeficiencyen_US
dc.subjectAsymmetryen_US
dc.subjectExposureen_US
dc.titleATP11C Facilitates Phospholipid Translocation across the Plasma Membrane of All Leukocytesen_US
dc.typeArticleen_US

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