title: ATP11C Facilitates Phospholipid Translocation across the Plasma Membrane of All Leukocytes.
abstract: Organization 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.
authors.affiliation: Department of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia.|Department of Genetics and Bioengineering, Faculty of Engineering, Trakya University, Edirne, Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Yabas
authors.affiliation: Division of Biomedical Science and Biochemistry, Research School of Biology, The Australian National University, Canberra, ACT, Australia.
authors.forename: Weidong
authors.initials: W
authors.lastname: Jing
authors.affiliation: Division of Biomedical Science and Biochemistry, Research School of Biology, The Australian National University, Canberra, ACT, Australia.
authors.forename: Sarah
authors.initials: S
authors.lastname: Shafik
authors.affiliation: Division of Biomedical Science and Biochemistry, Research School of Biology, The Australian National University, Canberra, ACT, Australia.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bröer
authors.affiliation: Department of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia.
authors.forename: Anselm
authors.initials: A
authors.lastname: Enders
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D001693:Biological Transport, Active / Q000502:physiology*; D002478:Cells, Cultured; D003609:Dactinomycin / Q000031:analogs & derivatives / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010714:Phosphatidylethanolamines / Q000378:metabolism*; D010718:Phosphatidylserines / Q000378:metabolism*; D049294:Phospholipid Transfer Proteins / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D010714:Phosphatidylethanolamines; D010718:Phosphatidylserines; D049294:Phospholipid Transfer Proteins; D003609:Dactinomycin; C483858:phosphatidylethanolamine; C025942:7-aminoactinomycin D; C000605549:ATP11C protein, mouse; D000251:Adenosine Triphosphatases