Cabral F, Barlow S B
Department of Pharmacology, University of Texas Medical School, Houston 77225.
Pharmacol Ther. 1991 Nov;52(2):159-71. doi: 10.1016/0163-7258(91)90006-8.
Much of our knowledge about microtubules has come from detailed morphological, biochemical, and cell biological studies. As more is learned about these organelles, questions regarding the in vivo regulation of their expression and function become increasingly important. Genetics provides an approach to address these more subtle questions in the living cell. Mammalian mutants with microtubule alterations have been isolated using selections for resistance to the cytotoxic effects of a number of antimitotic drugs. A subset of these mutants have clearly defined alterations in alpha- or in beta-tubulin, and these have been used to explore the mechanisms by which mammalian cells acquire resistance to this class of drugs. In addition, the mutants are providing valuable insights into how tubulin expression is regulated, into what factors determine the extent of microtubule assembly in living cells, into the domains of tubulin that are involved in assembly, and into the role of microtubules in essential cellular processes.
我们对微管的许多了解都来自详细的形态学、生物化学和细胞生物学研究。随着对这些细胞器的了解越来越多，关于其体内表达和功能调控的问题变得越来越重要。遗传学提供了一种在活细胞中解决这些更细微问题的方法。利用对多种抗有丝分裂药物细胞毒性作用的抗性筛选，已分离出具有微管改变的哺乳动物突变体。这些突变体的一个子集在α-或β-微管蛋白中具有明确界定的改变，并且这些已被用于探索哺乳动物细胞获得对这类药物抗性的机制。此外，这些突变体为微管蛋白表达如何被调控、哪些因素决定活细胞中微管组装的程度、参与组装的微管蛋白结构域以及微管在基本细胞过程中的作用提供了有价值的见解。
