Publication: [A lipid exchange market: vectorial cholesterol transport by the protein OSBP].

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Cholesterol is synthesized in the endoplasmic reticulum (ER) and then transported to cellular compartments whose functions require high cholesterol levels. Here, we describe the mechanism by which cholesterol is transported from the ER to the trans-Golgi network (TGN) by the protein OSBP (Oxysterol-Binding Protein). OSBP has two complementary activities. First, it tethers the RE to the TGN by forming a contact site where the two membranes are about twenty nanometers away. Then, it exchanges RE cholesterol for a TGN lipid, phosphatidylinositol 4-phosphate (PI4P). Eventually, PI4P is hydrolyzed at the RE, making the exchange cycle irreversible. Thus, OSBP is at the center of a lipid exchange market where a transported cholesterol «costs» a PI4P. Antiviral or anti-cancer molecules target OSBP, suggesting the importance of the OSBP cycle in different physiopathological contexts. The general principles of this cycle are shared by other lipid-transfer proteins. A lipid exchange market – Vectorial transport of cholesterol by the OSBP protein. Cholesterol is synthesized in the endoplasmic reticulum (ER) and then transported to cellular compartments whose function requires a high level of it. Here, we describe the mechanism of cholesterol transport from the ER to the trans-Golgi network (TGN) by the OSBP (oxysterol-binding protein). This protein has two complementary activities: it anchors the two compartments, ER and TGN, by forming a contact site where the two membranes are about twenty nanometers apart; then it exchanges cholesterol from the ER with a lipid present in the TGN, phosphatidylinositol 4-phosphate (PI4P). In the ER, PI4P is hydrolyzed, making the exchange cycle irreversible. OSBP is therefore at the heart of a lipid exchange market in which one transported cholesterol "costs" one PI4P. Molecules with antiviral or anticancer activities target OSBP, suggesting an importance in different pathophysiological contexts of the OSBP cycle, the general bases of which are shared by other lipid transport proteins.