Article abstract
Nature Cell Biology 1, 113 - 118 (1999)
Published online: 15 May 1999 | doi:10.1038/10084
Late endosomal membranes rich in lysobisphosphatidic acid regulate cholesterol transport
Toshihide Kobayashi1, Marie-Hélène Beuchat1, Margaret Lindsay2, Sonia Frias1, Richard D. Palmiter3, Hitoshi Sakuraba4, Robert G. Parton2 & Jean Gruenberg1
Abstract
The fate of free cholesterol released after endocytosis of low-density lipoproteins remains obscure. Here we report that late endosomes have a pivotal role in intracellular cholesterol transport. We find that in the genetic disease Niemann–Pick type C (NPC), and in drug-treated cells that mimic NPC, cholesterol accumulates in late endosomes and sorting of the lysosomal enzyme receptor is impaired. Our results show that the characteristic network of lysobisphosphatidic acid-rich membranes contained within multivesicular late endosomes regulates cholesterol transport, presumably by acting as a collection and distribution device. The results also suggest that similar endosomal defects accompany the anti-phospholipid syndrome and NPC.
- Department of Biochemistry, Sciences II, University of Geneva, 30 quai E. Ansermet, 1211. Geneva 4, Switzerland
- Center for Microscopy and Microanalysis, Center for Molecular and Cellular Biology and Department of Physiology and Pharmacology, University of Queensland, Queensland 4072, Australia
- Howard Hughes Medical Institute and Department of Biochemistry, Box 357370, University of Washington, Seattle, Washington 98195-7370, USA
- Department of Clinical Genetics, The Tokyo Metropolitan Institute of Medical Sciences, Bunkyo-ku, Tokyo 113, Japan
Correspondence to: Jean Gruenberg1 e-mail: jean.gruenberg@biochem.unige.ch
