A NOVEL CELL BIOLOGICAL APPROACH TO CONTROL HYPERLIPIDEMIA
Shadab A. Siddiqi, Samata Tiwari, Shaila Siddiqi
Biomedical Sciences, College of Medicine, University of Central Florida, USA
Increased secretion of very low-density lipoproteins (VLDL) by the liver causes hyperlipidemia, which is associated with obesity, type-2 diabetes and various cardiovascular diseases. The ratedetermining step in the secretion of VLDLs from the liver is their transport from the endoplasmic reticulum (ER) to the Golgi and represents a potential therapeutic target in controlling VLDL secretion. We have discovered a distinct ER-derived vesicle, VLDL transport vesicle (VTV), which
mediates the targeted delivery of VLDLs from the ER to the Golgi, however, factors regulating the
biogenesis of these vesicles remain un-identified. Our proteomic and biochemical analyses revealed that two small Mr proteins, cideB and SVIP are present in VTV but not in other ER-derived vesicles. Our co-immunoprecipitation data revealed that both cideB and SVIP specifically interact with VLDL structural protein, apolipoproteinB100. In current study, we investigated the roles of these proteins in VTV-biogenesis. To test their roles in VTV-biogenesis, we performed an in vitro ER-budding assay. We show that the blocking or knockdown of cideB and SVIP abrogates VTVbudding indicating their roles in VTV-biogenesis. We conclude that cideB and SVIP regulate VLDL secretion from the liver by controlling VTV-biogenesis and their identification is critical for the development of novel therapeutics for hyperlipidemia.