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

微管不寻常的聚合行为被称为动态不稳定性，被认为在形态发生中起重要作用。这种行为在体内是如何被调节的，人们知之甚少。实验旨在研究细胞中微管稳定性的全局调控，特别是研究部分ATP消耗和特定激酶和磷酸酶的微注射的影响。将寻找体外与微管结合的磷酸化依赖性或atp依赖性的其他蛋白质，并探索通过nocodazole敏感性（几乎所有先前分析的基础）测量的微管稳定性与通过掺入生物素标记的微管蛋白测量的稳定性之间的关系。进一步的研究计划确定体内稳定的微管是否在其末端被限制或通过沿着聚合物长度结合蛋白质来抑制解聚。微管相关蛋白和微管运动蛋白促进微管稳定性的详细机制将通过转染和生物素-微管蛋白注射来探索。在这些实验中，特定微管相关蛋白的结构研究将与微管生理调节的体内研究相结合，以期了解微管阵列的形态发生是如何产生的。“微管”是细胞内的亚微观结构，是决定细胞形状的内部“骨架”的组成部分。微管也充当轨道，其他亚细胞结构沿着它运动。微管是一种不稳定的结构，随着细胞内生理条件的变化而聚合或解聚。这项美苏合作研究涉及两位世界领先的微管结构和功能专家，研究控制微管稳定性的机制。这项合作研究的结果将提供重要的新信息，涉及决定细胞内微管形成位置、形成数量以及决定其长度的生化因素。这些知识将对我们对细胞功能的基本理解做出重要贡献。

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.