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

The EMBO Journal
Serena CapassoGiovanni D'Angelo

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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Citations

Feb 8, 2018·Nature Reviews. Molecular Cell Biology·Takeshi Harayama, Howard Riezman
Apr 4, 2018·Journal of Lipid Research·Justin M SniderYusuf A Hannun
Nov 23, 2017·Nature Reviews. Molecular Cell Biology·Yusuf A Hannun, Lina M Obeid
Aug 15, 2020·Frontiers in Cell and Developmental Biology·Nicolas-Frédéric LippGuillaume Drin
Mar 12, 2021·Current Opinion in Cell Biology·Bulat R RamazanovJulia von Blume
Mar 13, 2021·Current Opinion in Cell Biology·Pablo LujanFelix Campelo
Aug 29, 2020·Current Biology : CB·Noemi Jiménez-RojoHoward Riezman
Nov 7, 2020·The Journal of Cell Biology·Yuichi WakanaMitsuo Tagaya
May 20, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Bingen G MonasterioAlicia Alonso
May 27, 2021·Archives of Biochemistry and Biophysics·Pablo Lujan, Felix Campelo
Aug 3, 2021·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Anders P E Backman, Peter Mattjus
Aug 10, 2021·Frontiers in Cell and Developmental Biology·Petia AdarskaFrancesca Bottanelli
Aug 28, 2021·International Journal of Molecular Sciences·Yoko ItoYohann Boutté
Oct 7, 2020·Current Biology : CB·Britta Brügger

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