Journal of Lipid Research (Apr 2002)
Niemann-Pick C1 protein regulates cholesterol transport to the trans-Golgi network and plasma membrane caveolae
Abstract
The Niemann-Pick C1 (NPC1) protein regulates cholesterol transport from late endosomes-lysosomes to other intracellular compartments. In this article, cholesterol transport to caveolin-1 and caveolin-2 containing compartments, such as the trans-Golgi network (TGN) and plasma membrane caveolae, was examined in normal (NPC+/+), NPC heterozygous (NPC+/−), and NPC homozygous (NPCm/−) human fibroblasts. The expression and distribution of NPC1 in each cell type were similar, and characterized by a finely dispersed, granular staining pattern. The expression of caveolin-1 and caveolin-2 was increased in NPC+/− and NPC−/− fibroblasts, although the distribution in each cell type was similar and characterized by predominant staining of the TGN and plasma membrane. The TGN in NPC+/+ fibroblasts was relatively cholesterol-enriched, whereas the TGN in NPC+/− and NPC−/− fibroblasts was partially or completely cholesterol-deficient, respectively. Consistent with studies demonstrating the transport of cholesterol from the TGN to plasma membrane caveolae, the concentration of cholesterol in plasma membrane caveolae isolated from NPC+/− and NPC−/− fibroblasts was significantly decreased, even though the total concentration of plasma membrane cholesterol in each cell type was similar. These studies demonstrate that NPC1 regulates cholesterol transport to caveolin-1 and caveolin-2 containing compartments such as the TGN and plasma membrane caveolae.—Garver, W. S., K. Krishnan, J. R. Gallagos, M. Michikawa, G. A. Francis, and R. A. Heidenreich. Niemann-Pick C1 protein regulates cholesterol transport to the trans-Golgi network and plasma membrane caveolae. J. Lipid Res. 2002. 43: 579–589.
