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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1736-1754
Number of pages19
JournalEMBO Journal
Volume36
Issue number12
DOIs
Publication statusPublished - Jun 14 2017

Keywords

  • ceramide
  • lipid territories
  • lipid-transfer protein
  • membrane contact sites
  • PtdIns(4)P

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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  • Cite this

    Capasso, S., Sticco, L., Rizzo, R., Pirozzi, M., Russo, D., Dathan, N. A., Campelo, F., van Galen, J., Hölttä-Vuori, M., Turacchio, G., Hausser, A., Malhotra, V., Riezman, I., Riezman, H., Ikonen, E., Luberto, C., Parashuraman, S., Luini, A., & D'Angelo, G. (2017). Sphingolipid metabolic flow controls phosphoinositide turnover at the trans-Golgi network. EMBO Journal, 36(12), 1736-1754. https://doi.org/10.15252/embj.201696048