TY - JOUR T1 - Sphingolipid metabolic flow controls phosphoinositide turnover at the <em>trans</em> Golgi network JF - bioRxiv DO - 10.1101/090142 SP - 090142 AU - Serena Capasso AU - Lucia Sticco AU - Riccardo Rizzo AU - Marinella Pirozzi AU - Domenico Russo AU - Nina A. Dathan AU - Felix Campelo AU - Josse van Galen AU - Angelika Hausser AU - Vivek Malhotra AU - Seetharaman Parashuraman AU - Alberto Luini AU - Giovanni D’Angelo Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2016/11/28/090142.abstract N2 - 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. ER -