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The role of vesicular transport in ABCA1-dependent lipid efflux and its connection with NPC pathways

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Abstract

The membrane transporter ATP-binding cassette transporter A1 (ABCA1) has been shown to be the rate-limiting step in the initial formation of plasma high-density lipoprotein (HDL) particles. The mechanisms of action of ABCA1, including its role in the vesicular transport of lipids to the cell surface for the lipidation of HDL apolipoproteins, are not fully understood. Niemann–Pick type C (NPC) disease is most often caused by mutations in the NPC1 gene, whose protein product is believed to facilitate the egress of cholesterol and other lipids from late endosomes and lysosomes to other cellular compartments. This report reviews current knowledge regarding the role of ABCA1 in vesicular lipid transport mechanisms required for HDL particle formation, and the relationship between ABCA1 and NPC1 in this process.

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Abbreviations

HDL:

high-density lipoprotein

ABCA1:

ATP-binding cassette transporterA1

ApoA-I:

apolipoprotein A-I

NPC:

Niemann–Pick type C

PL:

phospholipids

C:

cholesterol

ER:

endoplasmic reticulum

TGN:

trans-Golgi network

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Acknowledgements

This work was supported by CIHR operating grant MOP-12660. The authors thank Drs. William Garver and John Oram for helpful discussions. This work was supported by a CIHR/HSFC/Pfizer Canada Training Fellowship in Stroke, Cardiovascular, Obesity, Lipid, and Atherosclerosis Research (SCOLAR) to E. Boadu. G.A. Francis is a Senior Scholar of the Alberta Heritage Foundation for Medical Research.

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Boadu, E., Francis, G.A. The role of vesicular transport in ABCA1-dependent lipid efflux and its connection with NPC pathways. J Mol Med 84, 266–275 (2006). https://doi.org/10.1007/s00109-005-0001-9

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