Cholesterol modulates membrane traffic along the endocytic pathway in sphingolipid-storage diseases

Puri, Vishwajeet; Watanabe, Rikio; Dominguez, Michel; Sun, Xinguo; Wheatley, Christine L.; Marks, David L.; Pagano, Richard E.

doi:10.1038/14084

Cited by 271 publications

(283 citation statements)

References 12 publications

(16 reference statements)

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“…Because the NPC1 protein has transmembrane domains, it is likely the diffuse cellular immunofluorescence under conditions of cholesterol depletion represents NPC1's diffuse distribution in an exten- sive membranous compartment, perhaps the endoplasmic reticulum. A similar effect of cellular cholesterol enrichment on NPC1 protein distribution was reported in an independent study (23). It should be noted that in these cholesterol-enriched cells, the NPC1 protein and cholesterol remain in separate and distinct LAMP-containing vesicles.…”

Section: Resultssupporting

confidence: 51%

Sterol-modulated Glycolipid Sorting Occurs in Niemann-Pick C1 Late Endosomes

Zhang¹,

Dwyer²,

Neufeld³

et al. 2001

Journal of Biological Chemistry

105

115

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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 cholesterolcontaining 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 GalNAc␤1-4[NeuAc␣2-3]Gal␤1-4Glc␤1-1-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, sterolmodulated sorting organelle involved in the trafficking of plasma membrane-derived glycolipids as well as plasma membrane and endocytosed LDL cholesterol.

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Section: Resultssupporting

confidence: 51%

Sterol-modulated Glycolipid Sorting Occurs in Niemann-Pick C1 Late Endosomes

Zhang¹,

Dwyer²,

Neufeld³

et al. 2001

Journal of Biological Chemistry

105

115

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“…Alternatively, it is also possible that the early endosomal GM1 accumulation is secondary to abnormal cholesterol trafficking in NPC cells. This hypothesis is supported by several lines of evidence that both intracellular levels and distribution of gangliosides could be modulated by cellular low-density lipoprotein uptake in NPC1-deficient CHO cells (7) as well as in normal human fibroblasts (26). It is the subject for future studies to test these hypotheses.…”

Section: Discussionmentioning

confidence: 54%

Accumulation of cholera toxin and GM1 ganglioside in the early endosome of Niemann–Pick C1-deficient cells

Sugimoto

Ninomiya

Ohsaki

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

100

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“…Because other factors may also contribute to detergent insolubility (see below), this may be an overestimation. The possibility that raft depletion does not impair internalization has been suggested from experiments examining PM-to-Golgi delivery of ricin, lactosylceramide, and cholera toxin (Puri et al, 1999;Rodal et al, 1999;Shogomori and Futerman, 2001). In all cases, no decreases in internalization were observed.…”

Section: Cholesterol and Glycosphingolipids Are Specifically Requiredmentioning

confidence: 94%

Transcytotic Efflux from Early Endosomes Is Dependent on Cholesterol and Glycosphingolipids in Polarized Hepatic Cells

Nyasae

Hubbard

Tuma

2003

MBoC

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We examined the role that lipid rafts play in regulating apical protein trafficking in polarized hepatic cells. Rafts are postulated to form in the trans-Golgi network where they recruit newly synthesized apical residents and mediate their direct transport to the apical plasma membrane. In hepatocytes, single transmembrane and glycolipid-anchored apical proteins take the "indirect" route. They are transported from the trans-Golgi to the basolateral plasma membrane where they are endocytosed and transcytosed to the apical surface. Do rafts sort hepatic apical proteins along this circuitous pathway? We took two approaches to answer this question. First, we determined the detergent solubility of selected apical proteins and where in the biosynthetic pathway insolubility was acquired. Second, we used pharmacological agents to deplete raft components and assessed their effects on basolateral-to-apical transcytosis. We found that cholesterol and glycosphingolipids are required for delivery from basolateral early endosomes to the subapical compartment. In contrast, fluid phase uptake and clathrin-mediated internalization of recycling receptors were only mildly impaired. Apical protein solubility did not correlate with raft depletion or impaired transcytosis, suggesting other factors contribute to apical protein insolubility. Examination of apical proteins in Fao cells also revealed that raft-dependent sorting does not require the polarized cell context.

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Cholesterol modulates membrane traffic along the endocytic pathway in sphingolipid-storage diseases

Cited by 271 publications

References 12 publications

Sterol-modulated Glycolipid Sorting Occurs in Niemann-Pick C1 Late Endosomes

Sterol-modulated Glycolipid Sorting Occurs in Niemann-Pick C1 Late Endosomes

Accumulation of cholera toxin and GM1 ganglioside in the early endosome of Niemann–Pick C1-deficient cells

Transcytotic Efflux from Early Endosomes Is Dependent on Cholesterol and Glycosphingolipids in Polarized Hepatic Cells

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