THE ANTI-APOPTOTIC PROTEIN BCL-XL ENHANCES NEURONAL METABOLISM

抗凋亡蛋白 BCL-XL 增强神经元代谢

• 批准号: 7598492
• 负责人: Elizabeth Ann Jonas
• 金额: $ 3.52万
• 依托单位: MARINE BIOLOGICAL LABORATORY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-01 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7598492
• 关键词: Apoptotic; Attenuated; Brain; Cell Death; Cell Survival; Cells; Computer Retrieval of Information on Scientific Projects Database; Cytosol; Event; Funding; Grant; Guanosine Triphosphate Phosphohydrolases; Hippocampus (Brain); Institution; Location; Membrane; Metabolism; Mitochondria; Mitochondrial Proteins; Neurons; Numbers; Oxygen; Presynaptic Terminals; Process; Proteins; Research; Research Personnel; Resources; Site; Source; Synapses; Transfection; United States National Institutes of Health; Vesicle; improved; postsynaptic; prevent; size; synaptogenesis

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. Within a developing presynaptic terminal, maturation of vesicle pools and synaptic stabilization occur shortly after contact with the postsynaptic target cell, but little is known about the intracellular molecules that control these processes. We have shown that the major brain anti-apoptotic mitochondrial protein BCL-xL acts presynaptically in cultured hippocampal neurons to increase the number and size of vesicle clusters, and to increase spontaneous vesicle fusion events. Normal mitochondrial function is necessary for the augmentation in spontaneous synaptic events because inhibition of mitochondrial function eliminates the increase. BCL-xL transfection increases the number of mitochondria and improves mitochondrial localization to synaptic sites in part through its effects on the GTPase DRP-1. Conversly, a reduction in endogenous BCL-xL decreases synaptogenesis without attenuating cell viability. Not only does BCL-xL direct newly divided mitochondria to synaptic sites, it also enhances ATP availability within the cytosol while decreasing oxygen flux across neuronal membranes. Thus, in addition to preventing cell death in neurons, we suggest that BCL-xL enhances mitochondrial efficiency and changes mitochondrial location, and may thereby produce synaptic maturation.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在发育中的突触前终末，囊泡池的成熟和突触的稳定发生在与突触后靶细胞接触后不久，但对控制这些过程的细胞内分子知之甚少。我们已经证明，脑中主要的抗凋亡线粒体蛋白BCL-XL作用于培养的海马神经元的突触前，增加囊泡团的数量和大小，并增加自发的囊泡融合事件。正常的线粒体功能对于自发突触事件的增强是必要的，因为抑制线粒体功能可以消除这种增加。BCL-XL基因通过对GTP酶DRP-1的影响，增加了线粒体的数量，改善了线粒体对突触部位的定位。相反，内源性bclxl的减少会减少突触的发生，而不会削弱细胞的活力。BCL-XL不仅将新分裂的线粒体定向到突触位置，它还提高了细胞质中ATP的可用性，同时减少了神经细胞膜的氧通量。因此，除了防止神经元细胞死亡外，我们认为bcl-xl还可以提高线粒体的效率并改变线粒体的位置，从而可能导致突触成熟。