RT Journal Article SR Electronic T1 Sphingolipid metabolic flow controls phosphoinositide turnover at the trans Golgi network JF bioRxiv FD Cold Spring Harbor Laboratory SP 090142 DO 10.1101/090142 A1 Serena Capasso A1 Lucia Sticco A1 Riccardo Rizzo A1 Marinella Pirozzi A1 Domenico Russo A1 Nina A. Dathan A1 Felix Campelo A1 Josse van Galen A1 Angelika Hausser A1 Vivek Malhotra A1 Seetharaman Parashuraman A1 Alberto Luini A1 Giovanni D’Angelo YR 2018 UL http://biorxiv.org/content/early/2016/11/28/090142.abstract AB Sphingolipids are membrane lipids, which are globally required for eukaryotic life. Sphingolipid composition varies among endomembranes with pre- and post-Golgi compartments being poor and rich in sphingolipids, respectively. Thanks to this different sphingolipid content, pre- and post-Golgi membranes serve different cellular functions. Nevertheless, how subcellular sphingolipid levels are maintained in spite of trafficking and metabolic fluxes is only partially understood. Here we describe a homeostatic control circuit that controls sphingolipid levels at the trans Golgi network. Specifically, we show that sphingomyelin production at the trans Golgi network triggers a signalling reaction 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 leads to the interruption of this transport in response to excessive sphingomyelin production. Based on this evidence we envisage a model where this homeostatic circuit maintains the sphingolipid composition of trans Golgi network and thus of post-Golgi compartments constant, against instant fluctuations in the sphingolipid biosynthetic flow.