ArticleJournal of cellular and molecular medicine2011
Role for LAMP-2 in endosomal cholesterol transport.
Article in Journal of cellular and molecular medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 95 citations in OpenAlex.
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- Mechanism and therapeutic potential of liver injury induced by cholesterol-associated proteins.Frontiers in pharmacology · 2025Review
- Altered fatty acid distribution in lysosome-associated membrane protein-2 deficient mice.Biochemistry and biophysics reports · 2024Article
- Endo-Lysosomal Network Disorder Reprograms Energy Metabolism in SorL1-Null Rat Hippocampus.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Differential roles of lysosomal cholesterol transporters in the development ofLife science alliance · 2024Article
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- Lysosomal LAMP proteins regulate lysosomal pH by direct inhibition of the TMEM175 channel.Molecular cell · 2023Article
- The Biology of Lysosomes: From Order to Disorder.Biomedicines · 2023Review
- Peanut lipids influence the response of bronchial epithelial cells to the peanut allergens Ara h 1 and Ara h 2 by decreasing barrier permeability.Frontiers in molecular biosciences · 2023Article
- Integrated multi-omics of the gastrointestinal microbiome and ruminant host reveals metabolic adaptation underlying early life development.Microbiome · 2022Article
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- BORC-ARL8-HOPS ensemble is required for lysosomal cholesterol egress through NPC2.Molecular biology of the cell · 2022Article
- Linking Late Endosomal Cholesterol with Cancer Progression and Anticancer Drug Resistance.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mechanisms of endosomal and lysosomal cholesterol traffic are still poorly understood. We showed previously that unesterified cholesterol accumulates in the late endosomes and lysosomes of fibroblasts deficient in both lysosome associated membrane protein-2 (LAMP-2) and LAMP-1, two abundant membrane proteins of late endosomes and lysosomes. In this study we show that in cells deficient in both LAMP-1 and LAMP-2 (LAMP(-/-)), low-density lipoprotein (LDL) receptor levels and LDL uptake are increased as compared to wild-type cells. However, there is a defect in esterification of both endogenous and LDL cholesterol. These results suggest that LAMP(-/-) cells have a defect in cholesterol transport to the site of esterification in the endoplasmic reticulum, likely due to defective export of cholesterol out of late endosomes or lysosomes. We also show that cholesterol accumulates in LAMP-2 deficient liver and that overexpression of LAMP-2 retards the lysosomal cholesterol accumulation induced by U18666A. These results point to a critical role for LAMP-2 in endosomal/lysosomal cholesterol export. Moreover, the late endosomal/lysosomal cholesterol accumulation in LAMP(-/-) cells was diminished by overexpression of any of the three isoforms of LAMP-2, but not by LAMP-1. The LAMP-2 luminal domain, the membrane-proximal half in particular, was necessary and sufficient for the rescue effect. Taken together, our results suggest that LAMP-2, its luminal domain in particular, plays a critical role in endosomal cholesterol transport and that this is distinct from the chaperone-mediated autophagy function of LAMP-2.
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