A proteolytic pathway that controls the cholesterol content of membranes, cells, and blood
TLDR
These regulated proteolytic cleavage reactions are ultimately responsible for controlling the level of cholesterol in membranes, cells, and blood.Abstract:
The integrity of cell membranes is maintained by a balance between the amount of cholesterol and the amounts of unsaturated and saturated fatty acids in phospholipids. This balance is maintained by membrane-bound transcription factors called sterol regulatory element-binding proteins (SREBPs) that activate genes encoding enzymes of cholesterol and fatty acid biosynthesis. To enhance transcription, the active NH2-terminal domains of SREBPs are released from endoplasmic reticulum membranes by two sequential cleavages. The first is catalyzed by Site-1 protease (S1P), a membrane-bound subtilisin-related serine protease that cleaves the hydrophilic loop of SREBP that projects into the endoplasmic reticulum lumen. The second cleavage, at Site-2, requires the action of S2P, a hydrophobic protein that appears to be a zinc metalloprotease. This cleavage is unusual because it occurs within a membrane-spanning domain of SREBP. Sterols block SREBP processing by inhibiting S1P. This response is mediated by SREBP cleavage-activating protein (SCAP), a regulatory protein that activates S1P and also serves as a sterol sensor, losing its activity when sterols overaccumulate in cells. These regulated proteolytic cleavage reactions are ultimately responsible for controlling the level of cholesterol in membranes, cells, and blood.read more
Citations
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Sterol homeostasis in the budding yeast, Saccharomyces cerevisiae.
TL;DR: The utilization of a genetically powerful model organism, budding yeast, is described here to identify and characterize novel aspects of sterol and lipid homeostasis.
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Interacting QTLs for cholesterol gallstones and gallbladder mucin in AKR and SWR strains of mice.
Henning Wittenburg,Frank Lammert,David Q.-H. Wang,Gary A. Churchill,Renhua Li,Guylaine Bouchard,Martin C. Carey,Beverly Paigen +7 more
TL;DR: New QTLs for cholesterol gallstones are uncovered, independent loci for mucin accumulation are revealed, and the importance of considering gene-gene interactions in cholesterol cholelithiasis is demonstrated.
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Altered Brain Cholesterol/Isoprenoid Metabolism in a Rat Model of Autism Spectrum Disorders.
Veronica Cartocci,Martina Catallo,Massimo Tempestilli,Marco Segatto,Frank W. Pfrieger,Maria Rosanna Bronzuoli,Caterina Scuderi,Michela Servadio,Viviana Trezza,Valentina Pallottini +9 more
TL;DR: VPA-treated rats present autistic-like symptoms, they show changes in cholesterol/isoprenoid homeostasis in some brain areas, a decreased number of oligodendrocytes and impaired myelination in the hippocampus, and this data suggest a relation between brain cholesterol/ isoprenoidsHomeostasis and ASDs.
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Enhanced circulating PCSK9 concentration by berberine through SREBP-2 pathway in high fat diet-fed rats.
TL;DR: The data provided the first line of the evidence that BBR, similar to the Sim, could increase the expression of PCSK9 levels in HFD rats through SREBP-2 activation, suggesting that impacts of BBR on lipid profile may also be linked to SRE BP-2 pathway.
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Physiologic and pathologic events mediated by intramembranous and juxtamembranous proteolysis.
TL;DR: This STKE review describes one of the more recently recognized ways in which cells transmit signals across lipid bilayers--through the action of proteases on proteins that span the membrane.
References
More filters
Journal ArticleDOI
A simple method for displaying the hydropathic character of a protein
Jack Kyte,Russell F. Doolittle +1 more
TL;DR: A computer program that progressively evaluates the hydrophilicity and hydrophobicity of a protein along its amino acid sequence has been devised and its simplicity and its graphic nature make it a very useful tool for the evaluation of protein structures.
Journal ArticleDOI
Functional rafts in cell membranes
Kai Simons,Elina Ikonen +1 more
TL;DR: A new aspect of cell membrane structure is presented, based on the dynamic clustering of sphingolipids and cholesterol to form rafts that move within the fluid bilayer that function as platforms for the attachment of proteins when membranes are moved around inside the cell and during signal transduction.
Journal ArticleDOI
The SREBP Pathway: Regulation of Cholesterol Metabolism by Proteolysis of a Membrane-Bound Transcription Factor
TL;DR: This research was supported by grants from the National Institutes of Health (HL20948) and the Perot Family Foundation.
Journal ArticleDOI
The Caveolae Membrane System
TL;DR: Caveolae constitute an entire membrane system with multiple functions essential for the cell and are capable of importing molecules and delivering them to specific locations within the cell, exporting molecules to extracellular space, and compartmentalizing a variety of signaling activities.
Journal ArticleDOI
Molecular cloning and expression of brain-derived neurotrophic factor.
Joachim Leibrock,Friedrich Lottspeich,Hohn Andreas,Magdalena Hofer,Bastian Hengerer,Piotr Masiakowski,Hans Thoenen,Yves-Alain Barde +7 more
TL;DR: The full primary structure of brain-derived neurotrophic factor is reported and it is established that these two neurotrophic factors are related both functionally and structurally.