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: 3121598
• 负责人: HELEN KIM
• 金额: $ 7.74万
• 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/3121598
• 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

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 某些微管群，以及制造新微管的能力 微管。 微管对于维持 成熟的神经元形态和功能。 衰老过程中观察到的异常现象 大脑（树突棘丧失、可塑性丧失）可能是由于 微管稳定性的异常调节。 从而了解 神经元形式和功能的调节至少部分取决于 了解调节微管组装的机制和 稳定。 由已乙酰化的微管蛋白组成的微管 已被证明更加稳定。 确定微管蛋白是否 乙酰化调节神经元的微管稳定性，我们将 在体外乙酰化脑微管，并确定它们是否 冷稳定性因效应而直接或间接改变 与微管相关蛋白的结合。 微管或 含有乙酰化微管蛋白的结构将进行形态学分析， 已经在冷稳定组分中进行了免疫化学和生物化学分析 在牛脑匀浆中鉴定为富含乙酰化 微管蛋白。 对于总概况，我们将量化总和乙酰化 微管蛋白，以及调节后者水平的酶，在 出生后大鼠大脑的发育、成熟和衰老。实验 诸如此类，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，以及它们是如何调节的 衰老和患病的大脑发生改变。