title: Role of tetanus neurotoxin insensitive vesicle-associated membrane protein in membrane domains transport and homeostasis.
abstract: Biological membranes in eukaryotes contain a large variety of proteins and lipids often distributed in domains in plasma membrane and endomembranes. Molecular mechanisms responsible for the transport and the organization of these membrane domains along the secretory pathway still remain elusive. Here we show that vesicular SNARE TI-VAMP/VAMP7 plays a major role in membrane domains composition and transport. We found that the transport of exogenous and endogenous GPI-anchored proteins was altered in fibroblasts isolated from VAMP7-knockout mice. Furthermore, disassembly and reformation of the Golgi apparatus induced by Brefeldin A treatment and washout were impaired in VAMP7-depleted cells, suggesting that loss of VAMP7 expression alters biochemical properties and dynamics of the Golgi apparatus. In addition, lipid profiles from these knockout cells indicated a defect in glycosphingolipids homeostasis. We conclude that VAMP7 is required for effective transport of GPI-anchored proteins to cell surface and that VAMP7-dependent transport contributes to both sphingolipids and Golgi homeostasis.
authors.affiliation: INSERM; U950; Membrane Traffic in Health and Disease ; Paris, France ; Univ Paris Diderot ; Sorbonne Paris Cité; ERL U950 ; Paris, France ; CNRS; UMR 7592; Institut Jacques Monod ; Paris, France ; Ecole Normale Supérieure-PSL Research University; Département de Chimie; Sorbonne Universités - UPMC Univ Paris 06 ; CNRS UMR 8640 PASTEUR ; Paris, France.
authors.forename: Diana
authors.initials: D
authors.lastname: Molino
authors.affiliation: INSERM; U950; Membrane Traffic in Health and Disease ; Paris, France ; Univ Paris Diderot ; Sorbonne Paris Cité; ERL U950 ; Paris, France ; CNRS; UMR 7592; Institut Jacques Monod ; Paris, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Nola
authors.affiliation: State Key Laboratory of Molecular Developmental Biology; Institute of Genetics and Developmental Biology; Chinese Academy of Sciences ; Beijing, China.
authors.forename: Sin Man
authors.initials: SM
authors.lastname: Lam
authors.affiliation: INSERM; U950; Membrane Traffic in Health and Disease ; Paris, France ; Univ Paris Diderot ; Sorbonne Paris Cité; ERL U950 ; Paris, France ; CNRS; UMR 7592; Institut Jacques Monod ; Paris, France.
authors.forename: Agathe
authors.initials: A
authors.lastname: Verraes
authors.affiliation: INSERM; U950; Membrane Traffic in Health and Disease ; Paris, France ; Univ Paris Diderot ; Sorbonne Paris Cité; ERL U950 ; Paris, France ; CNRS; UMR 7592; Institut Jacques Monod ; Paris, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Proux-Gillardeaux
authors.affiliation: Institut Curie ; CNRS UMR144 ; Paris, France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Boncompain
authors.affiliation: Institut Curie ; CNRS UMR144 ; Paris, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Perez
authors.affiliation: Department of Biochemistry; National University of Singapore; Yong Loo Lin School of Medicine ; Singapore.
authors.forename: Markus
authors.initials: M
authors.lastname: Wenk
authors.affiliation: State Key Laboratory of Molecular Developmental Biology; Institute of Genetics and Developmental Biology; Chinese Academy of Sciences ; Beijing, China.
authors.forename: Guanghou
authors.initials: G
authors.lastname: Shui
authors.affiliation: INSERM; U950; Membrane Traffic in Health and Disease ; Paris, France ; Univ Paris Diderot ; Sorbonne Paris Cité; ERL U950 ; Paris, France ; CNRS; UMR 7592; Institut Jacques Monod ; Paris, France.
authors.forename: Lydia
authors.initials: L
authors.lastname: Danglot
authors.affiliation: INSERM; U950; Membrane Traffic in Health and Disease ; Paris, France ; Univ Paris Diderot ; Sorbonne Paris Cité; ERL U950 ; Paris, France ; CNRS; UMR 7592; Institut Jacques Monod ; Paris, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Galli
keywords: BFA, Brefeldin A; Cer, Ceramide; ER, Endoplasmic Reticulum; GM3, ganglioside monosialic acid 3; GPI, Glycosylphosphatidylinositol; GSL, Glycosphingolipids; GlcCer, Glucosylceramide; Golgi apparatus; LC, Long Chain; PI, Phosphatidylinositide; PM, Plasma Membrane; SM, Sphingomyelin; SNARE; TGN, = Trans-Golgi Network; TI-VAMP/VAMP7; TI-VAMP/VAMP7, Tetanus neurotoxin-insensitive vesicle-associated membrane protein / Vesicle associated membrane protein 7; VLC, very long vhain; VSVG, Vesicular Stomatitis Virus Glycoprotein ; exocytosis; sphingolipids