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.
%0 Journal Article
%1 Capasso2017
%A Capasso, Serena
%A Sticco, Lucia
%A Rizzo, Riccardo
%A Pirozzi, Marinella
%A Russo, Domenico
%A Dathan, Nina A
%A Campelo, Felix
%A van Galen, Josse
%A Hölttä‐Vuori, Maarit
%A Turacchio, Gabriele
%A Hausser, Angelika
%A Malhotra, Vivek
%A Riezman, Isabelle
%A Riezman, Howard
%A Ikonen, Elina
%A Luberto, Chiara
%A Parashuraman, Seetharaman
%A Luini, Alberto
%A D'Angelo, Giovanni
%D 2017
%J The EMBO Journal
%K 2017 hausser izi
%N 12
%P 1736--1754
%R 10.15252/embj.201696048
%T Sphingolipid metabolic flow controls phosphoinositide turnover at the \textlessi\textgreatertrans\textless/i\textgreater ‐Golgi network
%U http://emboj.embopress.org/lookup/doi/10.15252/embj.201696048
%V 36
%X 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.
@article{Capasso2017,
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.},
added-at = {2018-02-01T14:25:43.000+0100},
author = {Capasso, Serena and Sticco, Lucia and Rizzo, Riccardo and Pirozzi, Marinella and Russo, Domenico and Dathan, Nina A and Campelo, Felix and van Galen, Josse and H{\"{o}}ltt{\"{a}}‐Vuori, Maarit and Turacchio, Gabriele and Hausser, Angelika and Malhotra, Vivek and Riezman, Isabelle and Riezman, Howard and Ikonen, Elina and Luberto, Chiara and Parashuraman, Seetharaman and Luini, Alberto and D'Angelo, Giovanni},
biburl = {https://puma.ub.uni-stuttgart.de/bibtex/2226556c901ac2d46debe62beb7c9f0c5/cristiano},
doi = {10.15252/embj.201696048},
interhash = {70a6343fcdf16a02793ecd90091d899b},
intrahash = {226556c901ac2d46debe62beb7c9f0c5},
issn = {0261-4189},
journal = {The EMBO Journal},
keywords = {2017 hausser izi},
month = jun,
number = 12,
pages = {1736--1754},
pmid = {28495678},
timestamp = {2018-07-25T12:32:13.000+0200},
title = {{Sphingolipid metabolic flow controls phosphoinositide turnover at the {\textless}i{\textgreater}trans{\textless}/i{\textgreater} ‐Golgi network}},
url = {http://emboj.embopress.org/lookup/doi/10.15252/embj.201696048},
volume = 36,
year = 2017
}
