Cholesterol Regulation of Lysosomes

溶酶体的胆固醇调节

• 批准号: 9888407
• 负责人: Suzanne R Pfeffer
• 金额: $ 39.25万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9888407
• 关键词: Acid Lipase; Atherosclerosis; Binding; Biochemical; Biogenesis; Biological; CD81 gene; Cardiovascular Diseases; Cell physiology; Cells; Cellular Membrane; Chemicals; Cholesterol; Complex; Cytoplasm; Data; Disease; Ebola virus; Glycoproteins; Goals; Harvest; LDL Cholesterol Lipoproteins; Lead; Link; Location; Low-Density Lipoproteins; Lysosomes; Malignant Neoplasms; Mediating; Membrane; Membrane Glycoproteins; Modeling; Molecular Conformation; Monitor; Mutation; NPC1 gene; Normal Cell; Pathway interactions; Physiological; Plasma; Probability; Process; Proteins; Regulation; Reporting; Research; Risk Factors; Signal Transduction; Sphingolipids; Sterols; Structure; Supraoptic Vertical Ophthalmoplegia; Testing; Work; cell growth regulation; cholesterol-binding protein; crosslink; experimental study; gain of function mutation; insight; limbic system-associated membrane protein; lysosome membrane; mutant; nervous system disorder; pathogenic virus; protein function; transcription factor

Project Summary The long term goal of this research is to understand how cholesterol gains access to intracellular compartments for utilization, storage and cellular regulation, via two glycoproteins: NPC1 and LAMP proteins. NPC1 is needed for the egress of endocytosed, LDL-derived cholesterol from lysosomes into the cytoplasm. LAMP proteins constitute the major glycoproteins that line the limiting membranes of lysosomes. The goal of this application is to study how these proteins may cooperate to transport cholesterol out of lysosomes, using biochemical and cell biological approaches. Experiments are proposed to investigate further, the cholesterol-dependent interaction between these proteins, and how they, and their interactions, may influence downstream activation of lysosome biogenesis. These experiments will provide important information regarding how cells may sense and signal the availability of cholesterol in lysosomes, and export cholesterol from lysosomes. This work has important implications for a number of disease states including cardiovascular disease, cancer, and neurological disorders.

项目总结

项目成果

CRISPR screens for lipid regulators reveal a role for ER-bound SNX13 in lysosomal cholesterol export.

• DOI: 10.1083/jcb.202105060
• 发表时间: 2022-02-07
• 期刊: The Journal of cell biology
• 作者: Lu A;Hsieh F;Sharma BR;Vaughn SR;Enrich C;Pfeffer SR
• 通讯作者: Pfeffer SR