title: Phospholipid scramblase-1-induced lipid reorganization regulates compensatory endocytosis in neuroendocrine cells.
abstract: Calcium-regulated exocytosis in neuroendocrine cells and neurons is accompanied by the redistribution of phosphatidylserine (PS) to the extracellular space, leading to a disruption of plasma membrane asymmetry. How and why outward translocation of PS occurs during secretion are currently unknown. Immunogold labeling on plasma membrane sheets coupled with hierarchical clustering analysis demonstrate that PS translocation occurs at the vicinity of the secretory granule fusion sites. We found that altering the function of the phospholipid scramblase-1 (PLSCR-1) by expressing a PLSCR-1 calcium-insensitive mutant or by using chromaffin cells from PLSCR-1⁻/⁻ mice prevents outward translocation of PS in cells stimulated for exocytosis. Remarkably, whereas transmitter release was not affected, secretory granule membrane recapture after exocytosis was impaired, indicating that PLSCR-1 is required for compensatory endocytosis but not for exocytosis. Our results provide the first evidence for a role of specific lipid reorganization and calcium-dependent PLSCR-1 activity in neuroendocrine compensatory endocytosis.
authors: Institut des Neurosciences Cellulaires et Intégratives, Centre National de la Recherche Scientifique-Unité Propre de Recherche 3212 and Université de Strasbourg, 67084 Strasbourg, France. ory@inci-cnrs.unistra.fr
authors: Stéphane
authors: S
authors: Ory
authors: Mara
authors: M
authors: Ceridono
authors: Fanny
authors: F
authors: Momboisse
authors: Sébastien
authors: S
authors: Houy
authors: Sylvette
authors: S
authors: Chasserot-Golaz
authors: Dimitri
authors: D
authors: Heintz
authors: Valérie
authors: V
authors: Calco
authors: Anne-Marie
authors: AM
authors: Haeberlé
authors: Flor A
authors: FA
authors: Espinoza
authors: Peter J
authors: PJ
authors: Sims
authors: Yannick
authors: Y
authors: Bailly
authors: Marie-France
authors: MF
authors: Bader
authors: Stéphane
authors: S
authors: Gasman
mesh_terms: D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D019439:Chromaffin Cells / Q000201:enzymology / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology*; D005089:Exocytosis / Q000502:physiology; D005260:Female; D050356:Lipid Metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D055099:Neuroendocrine Cells / Q000201:enzymology / Q000378:metabolism*; D016716:PC12 Cells; D010718:Phosphatidylserines / Q000378:metabolism*; D049294:Phospholipid Transfer Proteins / Q000378:metabolism*; D051381:Rats
chemical_list: D010718:Phosphatidylserines; D049294:Phospholipid Transfer Proteins; C493426:Plscr1 protein, mouse