Scientific article
English

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

Published inEMBO Journal, vol. 36, no. 12, p. 1736-1754
Publication date2017
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.

Keywords
  • Ceramide
  • Lipid territories
  • Lipid‐transfer protein
  • Membrane contact sites
  • PtdIns(4)P
Citation (ISO format)
CAPASSO, Serena et al. Sphingolipid metabolic flow controls phosphoinositide turnover at the trans‐Golgi network. In: EMBO Journal, 2017, vol. 36, n° 12, p. 1736–1754. doi: 10.15252/embj.201696048
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Article (Published version)
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Identifiers
Journal ISSN0261-4189
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