NPC1/NPC2 function as a tag team duo to mobilize cholesterol

Subramanian, Kanagaraj; Balch, William E.

doi:10.1073/pnas.0808256105

Cited by 84 publications

(78 citation statements)

References 24 publications

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“…Other data, however, have suggested that this protein cycles into the late endosomal/lysosomal compartment of cells (59) and may also actually mediate cholesterol movement from this organelle into the cytosolic compartment (60,61). Nearly every cell takes up lipoproteins containing either apoB 100 or apoE through receptor-mediated and bulk-phase endocytosis and processes the cholesteryl ester in these particles to unesterified cholesterol in the lysosome (11).…”

Section: Discussionmentioning

confidence: 99%

ABCA1 plays no role in the centripetal movement of cholesterol from peripheral tissues to the liver and intestine in the mouse

Xie

Turley

Dietschy

2009

Journal of Lipid Research

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This study uses the mouse to explore the role of ABCA1 in the movement of this cholesterol from the peripheral organs to the endocrine glands for hormone synthesis and liver for excretion. The sterol pool in all peripheral organs was constant and equaled 2,218 and 2,269 mg/kg, respectively, in abca1 1/1 and abca1 2/2 mice. Flux of cholesterol from these tissues equaled the rate of synthesis plus the rate of LDL-cholesterol uptake and was 49.9 mg/day/kg in control animals and 62.0 mg/day/kg in abca1 2/2 mice. In the abca1 1/1 animals, this amount of cholesterol moved from HDL into the liver for excretion. In the abca1 2/2 mice, the cholesterol from the periphery also reached the liver but did not use HDL. Fecal excretion of cholesterol was just as high in abac1 2/2 mice (198 mg/day/kg) as in the abac1animals (163 mg/day/kg), although the abac1 2/2 mice excreted relatively more neutral than acidic sterols. This study established that ABCA1 plays essentially no role in the turnover of cholesterol in peripheral organs or in the centripetal movement of this sterol to the endocrine glands, liver, and intestinal tract for excretion.-Xie, C., S. D. Turley, and J. M. Dietschy. ABCA1 plays no role in the centripetal movement of cholesterol from peripheral tissues to the liver and intestine in the mouse. J. Lipid Res. 2009Res. . 50: 1316Res. -1329

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Section: Discussionmentioning

confidence: 99%

ABCA1 plays no role in the centripetal movement of cholesterol from peripheral tissues to the liver and intestine in the mouse

Xie

Turley

Dietschy

2009

Journal of Lipid Research

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“…The animals present a null allele and are thus fully deficient in NPC1 protein [18,24]. This lysosomal transmembrane protein, together with the soluble NPC2 protein, is responsible for the efflux of free (unesterified) cholesterol from the late-endosomal/lysosomal compartment to the cytosol [52]. Deficiency in NPC1 protein leads to a massive accumulation of cholesterol in visceral organs of the mice.…”

Section: Modelmentioning

confidence: 99%

Lyso-glycosphingolipid abnormalities in different murine models of lysosomal storage disorders

Ferraz

Marques

Gaspar

et al. 2016

Molecular Genetics and Metabolism

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“…At this site of the endosomal membrane, cholesterol is bound by ORP5 (a transmembrane ER protein) and inserted into the ER membrane (Subramanian and Balch, 2008;Du et al, 2011) (Fig. 2).…”

Section: Protein Pairs At the Er-endosome Interfacementioning

confidence: 99%

Small regulators, major consequences – Ca2+ and cholesterol at the endosome–ER interface

Kant

Neefjes

2014

Journal of Cell Science

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The ER is the largest cellular compartment and a major storage site for lipids and ions. In recent years, much attention has focused on contacts between the ER and other organelles, and one particularly intimate relationship is that between the ER and the endosomal system. ER-endosome contacts intensify when endosomes mature, and the ER participates in endosomal processes, such as the termination of surface receptor signaling, multi-vesicular body formation, and transport and fusion events. Cholesterol and Ca 2+ are transferred between the ER and endosomes, possibly acting as messengers for ER-endosome crosstalk. Here, we summarize different types of ER-endosomal communication and discuss membrane contact sites that might facilitate this crosstalk. We review the protein pairs that interact at the ER-endosome interface and find that many of these have a role in cholesterol exchange. We also summarize Ca 2+ exchange between the ER and endosomes, and hypothesize that ERendosome contacts integrate several cellular functions to guide endosomal maturation. We post the hypothesis that failure in ERendosome contacts is an unrecognized but important contributor to diseases, such as Niemann-Pick type C disease, Alzheimer's disease and amyotrophic lateral sclerosis.

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NPC1/NPC2 function as a tag team duo to mobilize cholesterol

Cited by 84 publications

References 24 publications

ABCA1 plays no role in the centripetal movement of cholesterol from peripheral tissues to the liver and intestine in the mouse

ABCA1 plays no role in the centripetal movement of cholesterol from peripheral tissues to the liver and intestine in the mouse

Lyso-glycosphingolipid abnormalities in different murine models of lysosomal storage disorders

Small regulators, major consequences – Ca2+ and cholesterol at the endosome–ER interface

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