Phosphatidylserine transport by ORP/Osh proteins is driven by phosphatidylinositol 4-phosphate

• DOI: 10.1126/science.aab1346
• Publication Date: 2015-07-23T18:09:07Z
• Authors: Joachim Moser von...; Alenka Čopič; Vanessa Delfosse; Stefano Vanni; Catherine L. Jackson; William Bourguet; Guillaume Drin
• Keywords: Membrane contact site; Transport protein

In eukaryotic cells, phosphatidylserine (PS) is synthesized in the endoplasmic reticulum (ER) but highly enriched plasma membrane (PM), where it contributes negative charge and to specific recruitment of signaling proteins. This distribution relies on transport mechanisms whose nature remains elusive. Here, we found that PS transporter Osh6p extracted phosphatidylinositol 4-phosphate (PI4P) exchanged for PI4P between two membranes. We solved crystal structure Osh6p:PI4P complex demonstrated by depends recognition vivo. Finally, showed PI4P-phosphatase Sac1p, maintaining a gradient at ER/PM interface, drove transport. Thus, oxysterol-binding protein-related protein (ORP)/oxysterol-binding homology (Osh) proteins fueled metabolism through PS/PI4P exchange cycles.