Niemann-Pick C1 protein: obligatory roles for N-terminal domains and lysosomal targeting in cholesterol mobilization

The human Niemann-Pick type C (NPC) protein is studied to identify its structural features which are critical to intracellular cholesterol trafficking. The results show that in human fibroblasts, NPC1 protein is localized in a subset of vesicles containing LAMP2, a marker for late endosomes and lysosomes. Transient interactions with cholesterol laden lysosomes have been observed in wild-type NPC1-containing vesicles. Under experimental conditions, NPC1 appears to move through prelysosomal vesicles before entering the lysosomal compartment.