Cholesterol Regulates Syntaxin 6 Trafficking at trans-Golgi Network Endosomal Boundaries
Copyright policy )Cholesterol Regulates Syntaxin 6 Trafficking at trans-Golgi Network Endosomal Boundaries
Inhibition of cholesterol export from late endosomes causes cellular cholesterol imbalance, including cholesterol depletion in the trans-Golgi network (TGN). Here, using Chinese hamster ovary (CHO) Niemann-Pick type C1 (NPC1) mutant cell lines and human NPC1 mutant fibroblasts, we show that altered cholesterol levels at the TGN/endosome boundaries trigger Syntaxin 6 (Stx6) accumulation into VAMP3, transferrin, and Rab11-positive recycling endosomes (REs). This increases Stx6/VAMP3 interaction and interferes with the recycling of αVβ3 and α5β1 integrins and cell migration, possibly in a Stx6-dependent manner. In NPC1 mutant cells, restoration of cholesterol levels in the TGN, but not inhibition of VAMP3, restores the steady-state localization of Stx6 in the TGN. Furthermore, elevation of RE cholesterol is associated with increased amounts of Stx6 in RE. Hence, the fine-tuning of cholesterol levels at the TGN-RE boundaries together with a subset of cholesterol-sensitive SNARE proteins may play a regulatory role in cell migration and invasion.
- University of Sydney Australia
- Queensland University of Technology Australia
- University of Barcelona Spain
- UNSW Sydney Australia
- University of Barcelona (UB) Spain
Vesicle-Associated Membrane Protein 3, QH301-705.5, CHO Cells, Endosomes, Cricetulus, Cell Movement, Niemann-Pick C1 Protein, Cricetinae, Animals, Humans, Receptors, Vitronectin, Biology (General), Membrane Glycoproteins, Qa-SNARE Proteins, Intracellular Signaling Peptides and Proteins, Protein Transport, Cholesterol, rab GTP-Binding Proteins, Carrier Proteins, SNARE Proteins, Integrin alpha5beta1, Protein Binding
Vesicle-Associated Membrane Protein 3, QH301-705.5, CHO Cells, Endosomes, Cricetulus, Cell Movement, Niemann-Pick C1 Protein, Cricetinae, Animals, Humans, Receptors, Vitronectin, Biology (General), Membrane Glycoproteins, Qa-SNARE Proteins, Intracellular Signaling Peptides and Proteins, Protein Transport, Cholesterol, rab GTP-Binding Proteins, Carrier Proteins, SNARE Proteins, Integrin alpha5beta1, Protein Binding
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