ProjectLipid transfer at membrane contact sites
About
OSBP, a lipid transfer protein, is a fascinating molecular machine. First, OSBP transports a key cellular lipid, cholesterol. Second, OSBP is involved in pathological contexts such as viral infections and cancers. Third, through its various domains, OSBP performs two functions: transferring cholesterol and attaching the endoplasmic reticulum to the Golgi apparatus. In 2013, we succeeded in reconstructing this dual activity. Finally, a remarkable property of OSBP is its use of metabolic energy. We showed that OSBP and Osh4, its yeast homolog, exchange cholesterol for the phosphoinositide PI4P, which is then hydrolyzed by a phosphatase in the endoplasmic reticulum. Thus, PI4P acts as lipid ATP, allowing OSBP to transfer cholesterol in a directional manner. We continue our dissection of the OSBP cycle, focusing on its coupling with PI4-kinases and the numerous protein-protein and protein-membrane interactions involved. More generally, we are interested in the molecular architecture and dynamics of membrane contact sites and their role in lipid transport in pathophysiological contexts.
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| Reconstitution of a functional membrane contact site by OSBP | PI4P waves at Golgi after OSBP cycle disruption | |