VISUALIZATION OF BAX IN THE MEMBRANE

BAX 在膜中的可视化

• 批准号: 7723574
• 负责人: TOMOMI KUWANA
• 金额: $ 1.26万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7723574
• 关键词: Apoptosis; Caspase; Cells; Computer Retrieval of Information on Scientific Projects Database; Cytoplasm; Funding; Grant; Imagery; In Vitro; Institution; Lipid Bilayers; Liposomes; Malignant Neoplasms; Membrane; Mitochondria; Molecular; Outer Mitochondrial Membrane; Permeability; Protein Family; Proteins; Research; Research Personnel; Resources; Source; System; Therapeutic Intervention; United States National Institutes of Health; Vesicle

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. During apoptosis, mitochondria release intermembrane proteins to the cytoplasm to activate caspases and this step is critical. The Bcl-2 family proteins regulate the permeability of mitochondrial outer membrane, however, the molecular mechanisms of permeabilization is unclear. Visualization of lipid bilayer will aid our understanding of how Bcl-2 family proteins interact with the membrane. Apoptosis pathways are defective in most cancers and reactivation of them would be most logical in treatment. Most cells do not survive and prolifrerate after mitochondria are permeabilized, therefore, understanding of molecular mechanisms of mitochondrial outer membrane permeabilization is important for therapeutic intervention. We have developed in vitro vesicle systems (outer membrane vesicles and liposomes) to recapitulate membrane permeabilization by Bcl-2 family proteins, then tried to visualize the vesicles when permeabilization occurred. Conventional TEM didn't reveal any membrane changes in the outer membrane vesicles, suggesting the changes are subtle and transient. Cryo-EM is suited to capture transient changes, and could also be used to visualize molecules in the membrane.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 在凋亡过程中，线粒体将膜间蛋白释放到细胞质中以激活胱天蛋白酶，此步骤至关重要。 Bcl-2家族蛋白调节线粒体外膜的渗透性，但是，透化的分子机制尚不清楚。脂质双层的可视化将有助于我们理解Bcl-2家族蛋白如何与膜相互作用。 凋亡途径在大多数癌症中都是有缺陷的，在治疗中，它们的重新激活是最合乎逻辑的。大多数细胞在线粒体透化后无法生存，因此对线粒体外膜透化的分子机制的了解对于治疗干预很重要。 我们已经开发了体外囊泡系统（外膜外囊泡和脂质体），以概括Bcl-2家族蛋白的膜通透性，然后在发生通透性时尝试可视化囊泡。常规TEM没有揭示外膜外囊泡的任何膜变化，这表明这些变化是微妙和短暂的。冷冻EM适合捕获瞬态变化，也可以用于可视化膜中的分子。