title: Phospholipid Scramblase 1 Modulates FcR-Mediated Phagocytosis in Differentiated Macrophages.
abstract: Phospholipid Scramblase 1 (PLSCR1) was initially characterized as a type II transmembrane protein involved in bilayer movements of phospholipids across the plasma membrane leading to the cell surface exposure of phosphatidylserine, but other cellular functions have been ascribed to this protein in signaling processes and in the nucleus. In the present study, expression and functions of PLSCR1 were explored in specialized phagocytic cells of the monocyte/macrophage lineage. The expression of PLSCR1 was found to be markedly increased in monocyte-derived macrophages compared to undifferentiated primary monocytes. Surprisingly, this 3-fold increase in PLSCR1 expression correlated with an apparent modification in the membrane topology of the protein at the cell surface of differentiated macrophages. While depletion of PLSCR1 in the monocytic THP-1 cell-line with specific shRNA did not inhibit the constitutive cell surface exposure of phosphatidylserine observed in differentiated macrophages, a net increase in the FcR-mediated phagocytic activity was measured in PLSCR1-depleted THP-1 cells and in bone marrow-derived macrophages from PLSCR1 knock-out mice. Reciprocally, phagocytosis was down-regulated in cells overexpressing PLSCR1. Since endogenous PLSCR1 was recruited both in phagocytic cups and in phagosomes, our results reveal a specific role for induced PLSCR1 expression in the modulation of the phagocytic process in differentiated macrophages.
authors.affiliation: Inserm U1016, Institut Cochin, Paris, France.|CNRS, UMR8104, Paris, France.|Université Paris-Descartes, Sorbonne Paris-Cité, Paris, France.
authors.forename: Cecile
authors.initials: C
authors.lastname: Herate
authors.affiliation: Inserm U1016, Institut Cochin, Paris, France.|CNRS, UMR8104, Paris, France.|Université Paris-Descartes, Sorbonne Paris-Cité, Paris, France.
authors.forename: Ghania
authors.initials: G
authors.lastname: Ramdani
authors.affiliation: Institut des Neurosciences Cellulaires et Intégratives, CNRS UPR3212, and Université de Strasbourg, Strasbourg, France.
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Grant
authors.affiliation: Inserm U1016, Institut Cochin, Paris, France.|CNRS, UMR8104, Paris, France.|Université Paris-Descartes, Sorbonne Paris-Cité, Paris, France.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Marion
authors.affiliation: Institut des Neurosciences Cellulaires et Intégratives, CNRS UPR3212, and Université de Strasbourg, Strasbourg, France.
authors.forename: Stephane
authors.initials: S
authors.lastname: Gasman
authors.affiliation: Inserm U1016, Institut Cochin, Paris, France.|CNRS, UMR8104, Paris, France.|Université Paris-Descartes, Sorbonne Paris-Cité, Paris, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Niedergang
authors.affiliation: Inserm U1016, Institut Cochin, Paris, France.|CNRS, UMR8104, Paris, France.|Université Paris-Descartes, Sorbonne Paris-Cité, Paris, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Benichou
authors.affiliation: Inserm U1016, Institut Cochin, Paris, France.|CNRS, UMR8104, Paris, France.|Université Paris-Descartes, Sorbonne Paris-Cité, Paris, France.
authors.forename: Jerome
authors.initials: J
authors.lastname: Bouchet
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation; D006367:HeLa Cells; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D010587:Phagocytosis; D010718:Phosphatidylserines / Q000378:metabolism; D049294:Phospholipid Transfer Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D011961:Receptors, Fc / Q000378:metabolism*
chemical_list: D010718:Phosphatidylserines; D049294:Phospholipid Transfer Proteins; C493426:Plscr1 protein, mouse; D034741:RNA, Small Interfering; D011961:Receptors, Fc