“…Although increased t-SNARE endocytosis in AnxA6-overexpressing cells cannot be completely ruled out as contributing to the phenotype observed, the ability of AnxA6 to impact on SNARE localization and functioning is probably linked to its association with late endosomes, which plays a crucial role in cholesterol trafficking and homeostasis. Late endosomes are a sorting station and are capable of exporting cholesterol via vesicular (Maxfield and Tabas, 2005; Urano et al , 2008) and nonvesicular (protein-mediated) transport mechanisms involving NPC1 (Garver and Heidenreich, 2002) and cytoplasmic sterol-binding proteins (e.g., oxysterol-binding protein/OSBP-related proteins [OSBP/ORPs], ORP5; Ngo et al , 2010; Du et al , 2011) or through StAR-related lipid transfer domain (START)-domain proteins (Soccio and Breslow, 2003; Alpy and Tomasetto, 2005; Ikonen, 2008). In CHO-A6 cells, cholesterol accumulates in late endosomes, probably due to AnxA6 interference with NPC1 activity.…”