ArticleCellular and molecular life sciences : CMLS2020
Annexin A6 modulates TBC1D15/Rab7/StARD3 axis to control endosomal cholesterol export in NPC1 cells.
Article in Cellular and molecular life sciences : CMLS, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- Cholesterol homeostasis and cancer: a new perspective on the low-density lipoprotein receptor.Cellular oncology (Dordrecht, Netherlands) · 2022Pooled it
- Annexin A6 controls multi-organelle contact site formation and endolysosomal positioning, and remodels the STARD3 interactome.iScience · 2026Article
- Article
- Small Molecules to Elevate Rab7-GTPase Activity and Lower Cholesterol Accumulation in Niemann-Pick Type C Disease.Pharmaceutical research · 2026Article
- YY1 nitration participates in DbCM cardiomyocyte lipotoxicity by inhibiting ANXA3-induced microlipophagy.Redox biology · 2026Article
- Review
- Analyzing Endolysosome-Mitochondria Membrane Contact Sites by Thin Section TEM of Human Fibroblasts.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Inhibition of NPC Intracellular Cholesterol Transporter 1 Dually Regulates Aldosterone Secretion Via the Steroidogenic Acute Regulatory-Related Lipid Transfer Domain-3-Voltage-Dependent Anion Channel 1 Axis and Inositol 1,4,5-Trisphosphate Receptor Type 3-Calcium Signaling.Journal of the American Heart Association · 2025Article
- Fasting-Induced Hepatic Gluconeogenesis Is Compromised In Anxa6Journal of cellular physiology · 2025Article
- Revisiting the role of Annexins in membrane trafficking.Cellular and molecular life sciences : CMLS · 2025Review
- LRP1 immunotherapy enhances cardiomyocyte respiration by restricting cholesteryl ester accumulation in mitochondria.Journal of lipid research · 2025Article
- Targeting membrane contact sites to mediate lipid dynamics: innovative cancer therapies.Cell communication and signaling : CCS · 2025Review
- Lysosome-Mitochondrial Crosstalk in Cellular Stress and Disease.Antioxidants (Basel, Switzerland) · 2025Review
- Article
- Cholesterol and COVID-19-therapeutic opportunities at the host/virus interface during cell entry.Life science alliance · 2024Review
- Annexins-a family of proteins with distinctive tastes for cell signaling and membrane dynamics.Nature communications · 2024Review
- Novel strategies targeting mitochondria-lysosome contact sites for the treatment of neurological diseases.Frontiers in molecular neuroscience · 2024Review
- Regulating Cholesterol in Tumorigenesis: A Novel Paradigm for Tumor Nanotherapeutics.International journal of nanomedicine · 2024Review
- Niemann-Pick Disease Type C (NPDC) by Mutation ofAntioxidants (Basel, Switzerland) · 2023Review
- Intracellular Cholesterol Trafficking.Cold Spring Harbor perspectives in biology · 2023Review
Corrections and comments
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Authors and funding
20 authors at 9 institutions in 5 countries.
Funding
Abstract
Cholesterol accumulation in late endosomes is a prevailing phenotype of Niemann-Pick type C1 (NPC1) mutant cells. Likewise, annexin A6 (AnxA6) overexpression induces a phenotype reminiscent of NPC1 mutant cells. Here, we demonstrate that this cellular cholesterol imbalance is due to AnxA6 promoting Rab7 inactivation via TBC1D15, a Rab7-GAP. In NPC1 mutant cells, AnxA6 depletion and eventual Rab7 activation was associated with peripheral distribution and increased mobility of late endosomes. This was accompanied by an enhanced lipid accumulation in lipid droplets in an acyl-CoA:cholesterol acyltransferase (ACAT)-dependent manner. Moreover, in AnxA6-deficient NPC1 mutant cells, Rab7-mediated rescue of late endosome-cholesterol export required the StAR-related lipid transfer domain-3 (StARD3) protein. Electron microscopy revealed a significant increase of membrane contact sites (MCS) between late endosomes and ER in NPC1 mutant cells lacking AnxA6, suggesting late endosome-cholesterol transfer to the ER via Rab7 and StARD3-dependent MCS formation. This study identifies AnxA6 as a novel gatekeeper that controls cellular distribution of late endosome-cholesterol via regulation of a Rab7-GAP and MCS formation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.