Sphingolipid metabolic flow controls phosphoinositide turnover at the trans‐Golgi network |
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| Authors: | Serena Capasso Lucia Sticco Riccardo Rizzo Marinella Pirozzi Domenico Russo Nina A Dathan Felix Campelo Josse van Galen Maarit Hölttä‐Vuori Gabriele Turacchio Angelika Hausser Vivek Malhotra Isabelle Riezman Howard Riezman Elina Ikonen Chiara Luberto Seetharaman Parashuraman Alberto Luini Giovanni D'Angelo |
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| Institution: | 1. Istituto di Ricovero e Cura a Carattere Scientifico‐SDN, Naples, Italy;2. Institute of Protein Biochemistry‐National Research Council, Naples, Italy;3. ICFO‐Institut de Ciencies Fotoniques, The Barcelona Institute of Science and Technology, Barcelona, Spain;4. Centre for Genomic Regulation, The Barcelona Institute of Science and Technology, Barcelona, Spain;5. Universitat Pompeu Fabra, Barcelona, Spain;6. Department of Anatomy, Faculty of Medicine, Minerva Research Institute for Medical Research, University of Helsinki, Helsinki, Finland;7. Institute of Cell Biology and Immunology, University of Stuttgart, Stuttgart, Germany;8. Institució Catalana de Recerca i Estudis Avan?ats, Barcelona, Spain;9. Department of Biochemistry, NCCR Chemical Biology, University of Geneva, Geneva, Switzerland;10. Stony Brook Cancer Center, Health Science Center, Stony Brook University, Stony Brook, NY, USA |
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| 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. |
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| Keywords: | ceramide lipid territories lipid‐transfer protein membrane contact sites PtdIns(4)P |
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