Plasma membrane cholesterol homeostasis

The level of free intracellular cholesterol is strictly controlled by a wellcharacterized set of homeostatic mechanisms. In contrast, the mechanisms that control the intracellular distribution of sterols between various membranes within the cell are poorly understood. The majority (>95%) of cellular cholesterol resides in the plasma membrane and in endocytic vesicles derived from the plasma membrane. Here I describe my work designed to elucidate the mechanisms by which this intracellular distribution is developed and maintained. In Chapter 1, I review what is known about the intracellular distribution of cholesterol and the transport mechanisms that maintain these distributions. In Chapter 2, I describe the characterization of NPC fibroblasts, which have a defect in the transport of LDL-derived cholesterol from the endo/lysosomal compartment to the plasma membrane. I also describe the development and use of an assay to measure this transport process <italic>in vitro