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J. Biol. Chem., Vol. 281, Issue 42, 99932, October 20, 2006

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A New Cholesterol Transporter

Potential mechanisms of cholesterol transfer from NPC2 to membranes.

Niemann-Pick type C disease is a lipid storage disorder characterized by the accumulation of unesterified cholesterol and glycolipids in the endosomal/lysosomal system. The disease is caused by defects in either of two genes that code for the proteins NPC1 and NPC2. Although there is abundant indirect evidence that suggests a role for the NPC proteins in late endosomal/lysosomal transport of cholesterol, their precise functions at the cellular and molecular levels have not yet been determined.

NPC2 is a small intralysosomal protein that has been characterized biochemically as a cholesterol-binding protein. Using a fluorescence dequenching assay, Sunita R. Cheruku and colleagues monitored the kinetics of cholesterol transfer from NPC2 to model phospholipid membranes. They showed that transfer of cholesterol from NPC2 likely involves a collisional mechanism and is optimal in an acidic environment such as the endosomal/lysosomal compartment. They further demonstrated that NPC2 dramatically increases the rate of transfer of lyso-bisphosphatidic acid-containing vesicles. These studies support a role for the NPC2 protein in the transport of low density lipoprotein-derived cholesterol out of the endosomal/lysosomal compartment.

FOOTNOTES

See referenced article, J. Biol. Chem. 2006, 281, 31594-31604

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This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Related Collections Papers Of The Week Social Bookmarking                      What's this?