ACETYLATED TUBULIN IN DEVELOPING AND AGING RAT BRAIN

乙酰化微管蛋白在大鼠大脑发育和衰老中的作用

• 批准号: 3121596
• 负责人: HELEN KIM
• 金额: $ 8.09万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-01 至 1994-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3121596
• 关键词: Chlorophyta; acetylation; acyltransferase; aging; animal tissue; antibody; brain; chemical stability; cold temperature; cytoskeleton; developmental neurobiology; electron microscopy; enzyme mechanism; immunologic assay /test; laboratory rat; microtubule associated protein; microtubules; posttranslational modifications; protein purification; radiotracer; tissue /cell culture; tubulin; Chlorophyta; acetylation; acyltransferase; aging; animal tissue; antibody; brain; chemical stability; cold temperature; cytoskeleton; developmental neurobiology; electron microscopy; enzyme mechanism; immunologic assay /test; laboratory rat; microtubule associated protein; microtubules; posttranslational modifications; protein purification; radiotracer; tissue /cell culture; tubulin

Neuronal function and plasticity require the capacity to stabilize certain microtubule populations, as well as the ability to make new microtubules. Microtubules are also essential for the maintenance of mature neuronal form and function. Abnormalities observed in aging brain (loss of dendritic spines, loss of plasticity) may result from abnormal modulation of microtubule stability. Thus understanding the regulation of neuronal form and function will depend at least partially in understanding the mechanisms that regulate microtubule assembly and stability. Microtubules comprised of tubulin that has been acetylated have been shown to be more stable. To determine whether tubulin acetylation regulates microtubule stability in neurons, we will acetylate brain microtubules in vitro, and determine whether their cold-stability is altered either directly, or indirectly due to effects on the binding of microtubule-associated proteins. Microtubules or structures containg acetylated tubulin will be analyzed morphologically, immunochemically and biochemically in cold-stable fractions already identified in bovine brain homogenate as enriched for acetylated tubulin. For a total profile, we will quantify total and acetylated tubulin, and the enzymes that regulate the levels of the latter, during postnatal rat brain development, maturation, and senescence. Experiments such as these, that attempt to identify regulatory mechanisms in neuronal microtubule assembly, are essential for understanding the regulation of normal neuronal form and function, and how these may be altered in aged and diseased brain.

神经元功能和可塑性需要稳定的能力 某些微管种群以及制造新的能力 微管。 微管对于维护也是必不可少的 成熟的神经元形式和功能。 衰老中观察到的异常 大脑（树突状刺的丧失，可塑性的丧失）可能是由 微管稳定性的异常调制。 因此了解 神经元形式和功能的调节将至少部分取决于 了解调节微管组装的机制和 稳定。 由乙酰化的小管组成的微管 已被证明更稳定。 确定小管蛋白是否 乙酰化调节神经元中的微管稳定性，我们将 体外乙酰化脑脑微管，并确定其是否是否 由于影响，冷稳定性直接或间接改变 关于微管相关蛋白的结合。 微管或 遏制乙酰化小管蛋白的结构将在形态上分析， 在冷稳定性的部分中，免疫化学和生物化学上已经 在牛脑匀浆中鉴定为富集乙酰化的 微管蛋白。 对于总剖面，我们将量化总和乙酰化 微管蛋白和调节后者水平的酶 产后大鼠脑发育，成熟和衰老。实验 这样的尝试，试图确定监管机制 神经元微管组装，对于理解 正常神经元形式和功能的调节，以及这些可能如何 发生了变化的大脑和患病的大脑。