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Sphingolipid metabolic flow controls phosphoinositide turnover at the trans-Golgi network.

Authors
  • Capasso, Serena1
  • Sticco, Lucia2
  • Rizzo, Riccardo2
  • Pirozzi, Marinella2
  • Russo, Domenico2
  • Dathan, Nina A2
  • Campelo, Felix3, 4, 5
  • van Galen, Josse4, 5
  • Hölttä-Vuori, Maarit6
  • Turacchio, Gabriele2
  • Hausser, Angelika7
  • Malhotra, Vivek4, 5, 8
  • Riezman, Isabelle9
  • Riezman, Howard9
  • Ikonen, Elina6
  • Luberto, Chiara10
  • Parashuraman, Seetharaman2
  • Luini, Alberto1, 2
  • D'Angelo, Giovanni11, 2
  • 1 Istituto di Ricovero e Cura a Carattere Scientifico-SDN, Naples, Italy. , (Italy)
  • 2 Institute of Protein Biochemistry-National Research Council, Naples, Italy. , (Italy)
  • 3 ICFO-Institut de Ciencies Fotoniques, The Barcelona Institute of Science and Technology, Barcelona, Spain. , (Spain)
  • 4 Centre for Genomic Regulation, The Barcelona Institute of Science and Technology, Barcelona, Spain. , (Spain)
  • 5 Universitat Pompeu Fabra, Barcelona, Spain. , (Spain)
  • 6 Department of Anatomy, Faculty of Medicine, Minerva Research Institute for Medical Research, University of Helsinki, Helsinki, Finland. , (Finland)
  • 7 Institute of Cell Biology and Immunology, University of Stuttgart, Stuttgart, Germany. , (Germany)
  • 8 Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain. , (Spain)
  • 9 Department of Biochemistry, NCCR Chemical Biology, University of Geneva, Geneva, Switzerland. , (Switzerland)
  • 10 Stony Brook Cancer Center, Health Science Center, Stony Brook University, Stony Brook, NY, USA.
  • 11 Istituto di Ricovero e Cura a Carattere Scientifico-SDN, Naples, Italy [email protected] , (Italy)
Type
Published Article
Journal
The EMBO Journal
Publisher
EMBO
Publication Date
Jun 14, 2017
Volume
36
Issue
12
Pages
1736–1754
Identifiers
DOI: 10.15252/embj.201696048
PMID: 28495678
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Sphingolipids are membrane lipids globally required for eukaryotic life. The sphingolipid content varies among endomembranes with pre- and post-Golgi compartments being poor and rich in sphingolipids, respectively. Due to this different sphingolipid content, pre- and post-Golgi membranes serve different cellular functions. The basis for maintaining distinct subcellular sphingolipid levels in the presence of membrane trafficking and metabolic fluxes is only partially understood. Here, we describe a homeostatic regulatory circuit that controls sphingolipid levels at the trans-Golgi network (TGN). Specifically, we show that sphingomyelin production at the TGN triggers a signalling pathway leading to PtdIns(4)P dephosphorylation. Since PtdIns(4)P is required for cholesterol and sphingolipid transport to the trans-Golgi network, PtdIns(4)P consumption interrupts this transport in response to excessive sphingomyelin production. Based on this evidence, we envisage a model where this homeostatic circuit maintains a constant lipid composition in the trans-Golgi network and post-Golgi compartments, thus counteracting fluctuations in the sphingolipid biosynthetic flow. © 2017 The Authors.

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