Sterol-modulated glycolipid sorting occurs in niemann-pick C1 late endosomes - PubMed (original) (raw)

. 2001 Feb 2;276(5):3417-25.

doi: 10.1074/jbc.M005393200. Epub 2000 Oct 13.

N K Dwyer, E B Neufeld, D C Love, A Cooney, M Comly, S Patel, H Watari, J F Strauss 3rd, P G Pentchev, J A Hanover, E J Blanchette-Mackie

Affiliations

Free article

Sterol-modulated glycolipid sorting occurs in niemann-pick C1 late endosomes

M Zhang et al. J Biol Chem. 2001.

Free article

Abstract

The Niemann-Pick C1 (NPC1) protein and endocytosed low density lipoprotein (LDL)-derived cholesterol were shown to enrich separate subsets of vesicles containing lysosomal associated membrane protein 2. Localization of Rab7 in the NPC1-containing vesicles and enrichment of lysosomal hydrolases in the cholesterol-containing vesicles confirmed that these organelles were late endosomes and lysosomes, respectively. Lysobisphosphatidic acid, a lipid marker of the late endosomal pathway, was found in the cholesterol-enriched lysosomes. Recruitment of NPC1 to Rab7 compartments was stimulated by cellular uptake of cholesterol. The NPC1 compartment was shown to be enriched in glycolipids, and internalization of GalNAcbeta1-4[NeuAcalpha2-3]Galbeta1-4Glcbeta1-1'-ceramide (G(M2)) into endocytic vesicles depends on the presence of NPC1 protein. The glycolipid profiles of the NPC1 compartment could be modulated by LDL uptake and accumulation of lysosomal cholesterol. Expression in cells of biologically active NPC1 protein fused to green fluorescent protein revealed rapidly moving and flexible tubular extensions emanating from the NPC1-containing vesicles. We conclude that the NPC1 compartment is a dynamic, sterol-modulated sorting organelle involved in the trafficking of plasma membrane-derived glycolipids as well as plasma membrane and endocytosed LDL cholesterol.

PubMed Disclaimer

Similar articles

Cited by

MeSH terms

Substances

LinkOut - more resources