Cholesterol-binding molecules MLN64 and ORP1L mark distinct late endosomes with transporters ABCA3 and NPC1

Cholesterol is an essential lipid in eukaryotic cells and is present in membranes of all intracellular compartments. A major source for cellular cholesterol is internalized lipoprotein particles that are transported toward acidic late endosomes (LE) and lysosomes. Here the lipoprotein particles are...

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Main Authors: Rik van der Kant, Ilse Zondervan, Lennert Janssen, Jacques Neefjes
Format: Article
Language:English
Published: Elsevier 2013-08-01
Series:Journal of Lipid Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0022227520375313
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spelling doaj-5fc32b50c5c34a47995e761a8cd543a92021-04-28T06:02:12ZengElsevierJournal of Lipid Research0022-22752013-08-0154821532165Cholesterol-binding molecules MLN64 and ORP1L mark distinct late endosomes with transporters ABCA3 and NPC1Rik van der Kant0Ilse Zondervan1Lennert Janssen2Jacques Neefjes3Division of Cell Biology, Netherlands Cancer Institute, Amsterdam, NetherlandsDivision of Cell Biology, Netherlands Cancer Institute, Amsterdam, NetherlandsDivision of Cell Biology, Netherlands Cancer Institute, Amsterdam, NetherlandsTo whom correspondence should be addressed; Division of Cell Biology, Netherlands Cancer Institute, Amsterdam, NetherlandsCholesterol is an essential lipid in eukaryotic cells and is present in membranes of all intracellular compartments. A major source for cellular cholesterol is internalized lipoprotein particles that are transported toward acidic late endosomes (LE) and lysosomes. Here the lipoprotein particles are hydrolyzed, and free cholesterol is redistributed to other organelles. The LE can contain over half of the cellular cholesterol and, as a major sorting station, can contain many cholesterol-binding proteins from the ABCA, STARD, and ORP families. Here, we show that metastatic lymph node 64 (MLN64, STARD3) and oxysterol-binding protein-related protein 1L (ORP1L) define two subpopulations of LE. MLN64 is present on a LE containing the cholesterol transporter ABCA3, whereas ORP1L localizes to another population of LE containing Niemann Pick type C1 (NPC1), a cholesterol exporter. Endocytosed cargo passes through MLN64/ABCA3-positive compartments before it reaches ORP1L/NPC1-positive LE. The MLN64/ABCA3 compartments cycle between LE and plasma membrane and frequently contact “later” ORP1L/NPC1-containing LE. We propose two stages of cholesterol handling in late endosomal compartments: first, cholesterol enters MLN64/ABCA3-positive compartments from where it can be recycled to the plasma membrane, and later, cholesterol enters ORP1L/NPC1 endosomes that mediate cholesterol export to the endoplasmic reticulum.http://www.sciencedirect.com/science/article/pii/S0022227520375313lysosomemetastatic lymph node 64oxysterol-binding protein-related protein 1LATP binding cassette transporter A3Niemann Pick disease type C1STARD3
collection DOAJ
language English
format Article
sources DOAJ
author Rik van der Kant
Ilse Zondervan
Lennert Janssen
Jacques Neefjes
spellingShingle Rik van der Kant
Ilse Zondervan
Lennert Janssen
Jacques Neefjes
Cholesterol-binding molecules MLN64 and ORP1L mark distinct late endosomes with transporters ABCA3 and NPC1
Journal of Lipid Research
lysosome
metastatic lymph node 64
oxysterol-binding protein-related protein 1L
ATP binding cassette transporter A3
Niemann Pick disease type C1
STARD3
author_facet Rik van der Kant
Ilse Zondervan
Lennert Janssen
Jacques Neefjes
author_sort Rik van der Kant
title Cholesterol-binding molecules MLN64 and ORP1L mark distinct late endosomes with transporters ABCA3 and NPC1
title_short Cholesterol-binding molecules MLN64 and ORP1L mark distinct late endosomes with transporters ABCA3 and NPC1
title_full Cholesterol-binding molecules MLN64 and ORP1L mark distinct late endosomes with transporters ABCA3 and NPC1
title_fullStr Cholesterol-binding molecules MLN64 and ORP1L mark distinct late endosomes with transporters ABCA3 and NPC1
title_full_unstemmed Cholesterol-binding molecules MLN64 and ORP1L mark distinct late endosomes with transporters ABCA3 and NPC1
title_sort cholesterol-binding molecules mln64 and orp1l mark distinct late endosomes with transporters abca3 and npc1
publisher Elsevier
series Journal of Lipid Research
issn 0022-2275
publishDate 2013-08-01
description Cholesterol is an essential lipid in eukaryotic cells and is present in membranes of all intracellular compartments. A major source for cellular cholesterol is internalized lipoprotein particles that are transported toward acidic late endosomes (LE) and lysosomes. Here the lipoprotein particles are hydrolyzed, and free cholesterol is redistributed to other organelles. The LE can contain over half of the cellular cholesterol and, as a major sorting station, can contain many cholesterol-binding proteins from the ABCA, STARD, and ORP families. Here, we show that metastatic lymph node 64 (MLN64, STARD3) and oxysterol-binding protein-related protein 1L (ORP1L) define two subpopulations of LE. MLN64 is present on a LE containing the cholesterol transporter ABCA3, whereas ORP1L localizes to another population of LE containing Niemann Pick type C1 (NPC1), a cholesterol exporter. Endocytosed cargo passes through MLN64/ABCA3-positive compartments before it reaches ORP1L/NPC1-positive LE. The MLN64/ABCA3 compartments cycle between LE and plasma membrane and frequently contact “later” ORP1L/NPC1-containing LE. We propose two stages of cholesterol handling in late endosomal compartments: first, cholesterol enters MLN64/ABCA3-positive compartments from where it can be recycled to the plasma membrane, and later, cholesterol enters ORP1L/NPC1 endosomes that mediate cholesterol export to the endoplasmic reticulum.
topic lysosome
metastatic lymph node 64
oxysterol-binding protein-related protein 1L
ATP binding cassette transporter A3
Niemann Pick disease type C1
STARD3
url http://www.sciencedirect.com/science/article/pii/S0022227520375313
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AT ilsezondervan cholesterolbindingmoleculesmln64andorp1lmarkdistinctlateendosomeswithtransportersabca3andnpc1
AT lennertjanssen cholesterolbindingmoleculesmln64andorp1lmarkdistinctlateendosomeswithtransportersabca3andnpc1
AT jacquesneefjes cholesterolbindingmoleculesmln64andorp1lmarkdistinctlateendosomeswithtransportersabca3andnpc1
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