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- Sterols regulate ER-to-Golgi transport of SREBP cleavage activating protein (SCAP)
- Espenshade, Peter J.
- Presents Cholesterol homeostasis in mammalian cells is regulated at the level of transcription through feedback inhibition. When cells are depleted of sterols, transcription of genes required for synthesis and uptake of cholesterol, such as HMG-CoA reductase (HMGR) and LDL receptor, is upregulated by a family of ER membrane-bound transcription factors called sterol regulatory element binding proteins, SREBP. The N terminus of SREBP is a basic helix-loop-helix leucine zipper transcription factor and the C terminus binds tightly to SREBP cleavage activating protein (SCAP). In sterol-replete cells, the SREBP-SCAP complex remains in the ER, compartmentally separated from the Golgi-localized Site-1 and Site-2 proteases. ER retention of SREBP-SCAP is mediated by the sterol-dependent binding of SREBP-SCAP to the ER resident protein Insig. In the first video, sterol-replete Chinese Hamster Ovary cells stably expressing GFP-SCAP were imaged in the presence of excess sterol that inhibits ER-to-Golgi transport of SCAP. In sterol-depleted cells, SCAP does not bind Insig, allowing ER exit of SREBP-SCAP via COPII vesicles. Transport to the Golgi results in SREBP cleavage by Site-1 and Site-2 proteases and release of the N-terminal transcription factor domain from the membrane. Activated SREBP enters the nucleus and upregulates genes required for cholesterol supply. Following SREBP cleavage, SCAP is thought to recycle from the Golgi to the ER in order to participate in additional rounds of SREBP proteolysis. In the second video, cells were acutely depleted of cholesterol at t=0 to induce SCAP transport to the Golgi. GFP-SCAP first appears in vesicular structures and then clearly accumulates in the Golgi by t=15 min
- Componente Curricular::Educação Superior::Ciências Biológicas::Biologia Geral
- The American Society for Cell Biology, ASBC Image & Video Library
- Mammalian cell
- Educação Superior::Ciências Biológicas::Biologia Geral
- To show the cholesterol homeostasis in mammalian cells
- Duration: 59 s. Contributors: Axel Nohturfft, Joseph L. Goldstein, Michael S. Brown. To visualize this source its necessary the instalation of Quick time. Available at: <http://www.apple.com/pt/quicktime/>
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