How does lipid transport between organelles in the cell take place and how is it regulated? A lesson from the ceramide transport protein CERT

About the talk: Lipids are the major constituents of all cell membranes and play dynamic roles in organelle structure and function. In eukaryotic cells, the endoplasmic reticulum (ER) is the main center for the synthesis of diverse types of lipids. In mammalian cells, ceramide is newly synthesized in the ER and converted to sphingomyelin in the distal Golgi regions. In 2003, we showed that the ceramide transport protein CERT is the molecular machinery for the non-vesicular transport of ceramide. Then, in these two decades, it has been elucidated that various lipids synthesized in the ER are rapidly and accurately delivered to other organelles by a variety of lipid transfer proteins (LTPs) at zones where the ER is in contact with other specific organelles. However, how the function of LTPs is regulated and what pathophysiological consequences occur after dysregulation of LTPs remains poorly understood. Moreover, the repertoire of specific LTP inhibitors is limited although LTPs have been gaining attention as a novel type of molecular medicinal target.In this Centenary Institute Tuesday Seminar, I would like to present the following four topics: 1) The early history of CERT and a mechanistic consideration of rapid and accurate inter-organelle transport of lipids at organelle membrane contact zones, 2) phospho-regulation of CERT, 3) dysregulation of CERT causes certain hereditary mental disorders, and 4) development of natural ligand-mimetic and non-mimetic inhibitors of CERT.