US-Commonwealth of Independent States Cooperative Research on Regulation of Microtubule Stability

美国-独联体微管稳定性调控合作研究

• 批准号: 9016667
• 负责人: Marc Kirschner
• 金额: --
• 依托单位: University of California-San Francisco
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-07-01 至 1994-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9016667&HistoricalAwards=false
• 关键词: US; Commonwealth; Independent; States; Cooperative

The unusual polymerization behavior of microtubules known as dynamic instability is thought to play an important role in morphogenesis. The means by which this behavior is regulated in vivo is very poorly understood. Experiments are proposed to look at global regulation of microtubule stability in cells, and in particular to look at the effect of partial ATP depletion and microinjection of specific kinases and phosphatases. Additional proteins that show phosphorylation-dependent or ATP-dependent binding to microtubules in vitro will be sought, and the relationship of microtubule stability as measured by nocodazole sensitivity (the basis for almost all previous analyses), and stability, as measured by the incorporation of biotin-labelled tubulin, will be explored. Further studies are planned to determine whether stable microtubules in vivo are capped at their ends or inhibited from depolymerization by binding of proteins along the length of the polymer. The detailed mechanisms by which microtubule associated proteins and microtubule motor proteins contribute to microtubule stability will be explored by transfection and biotin-tubulin injection. In these experiments a study of the structure of specific microtubule-associated proteins will be combined with in vivo studies of physiological regulation of microtubules in the hope of understanding how the morphogenesis of microtubule arrays is generated. "Microtubules" are sub-microscopic structures, small tubes, within cells that serve as a component of the internal "skeleton" that determines a cell's shape. Microtubules also serve as tracks, along which other sub-cellular structures move. Microtubules are unstable structures that polymerize or depolymerize in response to changing physiological conditions within the cell. This US-USSR cooperative research involves two of the world's leading experts on microtubule structure and function in a study of the mechanisms that control microtubule stability. The results of this collaborative research should provide important new information concerning the biochemical factors that determine where, within cells, microtubules form, how many form, and what determines their length. This knowledge will be an important contribution to our fundamental understanding of how cells function.

微管不寻常的聚合行为被称为 动力不稳定性被认为在 形态发生 这种行为的调节方式， 对vivo的了解非常少。 实验是为了寻找 在细胞中微管稳定性的全局调节， 特别是看看部分ATP消耗的影响， 显微注射特定的激酶和磷酸酶。 额外 显示磷酸化依赖或ATP依赖的蛋白质 将寻求与体外微管的结合， 用诺考达唑测定微管稳定性的关系 敏感性（几乎所有先前分析的基础），以及 通过掺入生物素标记的 tubulin，将被探索。 计划开展进一步研究， 确定体内稳定的微管是否在其 通过蛋白质结合终止或抑制解聚 沿着聚合物的长度。 详细的机制， 微管相关蛋白和微管马达蛋白 有助于微管稳定性将探索 转染和生物素-微管蛋白注射。 在这些实验中 特定微管相关蛋白结构的研究 蛋白质将与生理学的体内研究相结合， 微管的调节，希望了解 产生微管阵列的形态发生。 “微管”是亚微观结构，小管， 细胞作为内部“骨架”的组成部分， 决定了细胞的形状 微管也可以作为轨道， 其他亚细胞结构沿着沿着移动。 微管是 不稳定的结构， 改变细胞内的生理条件。 这个美苏 合作研究涉及两个世界领先的 微管结构和功能的专家在一项研究中， 控制微管稳定性的机制。 的结果 合作研究应该提供重要的新信息 关于决定在哪里， 细胞，微管的形式，有多少形式，是什么决定了它们的 长度 这些知识将对我们的研究做出重要贡献。 对细胞功能的基本理解