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- W4386935171 abstract "Abstract Abnormal distribution of cellular cholesterol is associated with numerous diseases, including cardiovascular and neurodegenerative diseases. Regulated transport of cholesterol is critical for maintaining its proper distribution in the cell, yet the underlying mechanisms remain unclear. Here, we show that lipid transfer proteins, namely ORP9, OSBP, and GRAMD1s/Asters (GRAMD1a/GRAMD1b/GRAMD1c), control non-vesicular cholesterol transport at points of contact between the ER and the trans-Golgi network (TGN), thereby maintaining cellular cholesterol distribution. ORP9 localizes to the TGN via interaction between its tandem α-helices and ORP10/ORP11. ORP9 extracts PI4P from the TGN to prevent its overaccumulation and suppresses OSBP-mediated PI4P-driven cholesterol transport to the Golgi. By contrast, GRAMD1s transport excess cholesterol from the Golgi to the ER, thereby preventing its build-up. Cells lacking ORP9 exhibit accumulation of cholesterol at the Golgi, which is further enhanced by additional depletion of GRAMD1s with major accumulation in the plasma membrane. This is accompanied by chronic activation of the SREBP-2 signalling pathway. Our findings reveal the importance of regulated lipid transport at ER-Golgi contacts for maintaining cellular cholesterol distribution and homeostasis." @default.
- W4386935171 created "2023-09-22" @default.
- W4386935171 creator A5012491939 @default.
- W4386935171 creator A5015142199 @default.
- W4386935171 creator A5019198817 @default.
- W4386935171 creator A5047427629 @default.
- W4386935171 creator A5061335959 @default.
- W4386935171 creator A5064942934 @default.
- W4386935171 date "2023-09-21" @default.
- W4386935171 modified "2023-10-16" @default.
- W4386935171 title "Regulation of cellular cholesterol distribution via non-vesicular lipid transport at ER-Golgi contact sites" @default.
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