The glycolipid transfer protein GLTP as a mediator of vesicular transport of ceramide

The glycolipid transfer protein (GLTP) is linked to a multitude of cellular processes aside from its best-known function as a lipid transport protein. Based on previous research and hypotheses, it is for example proposed that it may also act as a sensor and regulator of glycolipid homeostasis in the cell, as expression levels of GLTP directly influence the cellular levels of many glycosphingolipid species. Furthermore, through its previously determined interaction with the ER membrane protein VAP—A (vesicle-associated membrane protein-associated protein A), GLTP may also be involved in facilitating or regulating vesicular transport in the cell. In this study, we propose a role of GLTP in regulating the COPII vesicle trafficking pathway and thereby indirectly regulating the glycosphingolipid homeostasis of the cell, by regulating the vesicular ceramide transport from the ER to the Golgi apparatus. We propose that the effect of GLTP expression levels on the glycolipid homeostasis is related to the observed effect of GLTP on vesicle trafficking; ceramide for GSL synthesis is likely primarily transferred from the ER to the Golgi through vesicular transport, and the observed effects of GLTP fit this hypothesis. The restriction of GLTP/VAP—A-interaction by GLTP-GSL binding may provide a regulatory mechanism. We also show that GLTP localizes to the nucleus of the cell at the onset of the S-phase of the cell cycle, an unexpected discovery which further complicates our understanding of the function of GLTP.