Department of Cell Biology and Genetics, Erasmus MC, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
Curr Biol. 2010 Jun 22;20(12):R528-37. doi: 10.1016/j.cub.2010.05.022.
Microtubules are cytoskeletal elements that are essential for a large number of intracellular processes, including mitosis, cell differentiation and migration, and vesicle transport. In many cells, the microtubule network is organized in a radial manner, with one end of a microtubule (the minus end) embedded near the nucleus and the other end (the plus end) exploring cytoplasmic space, switching between episodes of growth and shrinkage. Mammalian plus-end-tracking proteins (+TIPs) localize to the ends of growing microtubules and regulate both the dynamic behavior of microtubules as well as the interactions of microtubules with other cellular components. Because of these crucial roles, +TIPs and the mechanisms underlying their association with microtubule ends have been intensively investigated. Results indicate that +TIPs reach microtubule ends by motor-mediated transport or diffusion. Individual +TIP molecules exchange rapidly on microtubule end-binding sites that are formed during microtubule polymerization and that have a slower turnover. Most +TIPs associate with the end-binding (EB) proteins, and appear to require these 'core' +TIPs for localization at microtubule ends. Accumulation of +TIPs may also involve structural features of the microtubule end and interactions with other +TIPs. This complexity makes it difficult to assign discrete roles to specific +TIPs. Given that +TIPs concentrate at microtubule ends and that each +TIP binds in a conformationally distinct manner, I propose that the ends of growing microtubules are 'nano-platforms' for productive interactions between selected proteins and that these interactions might persist and be functional elsewhere in the cytoplasm than at the microtubule end at which they originated.
微管是细胞骨架的组成部分，对于许多细胞内过程至关重要，包括有丝分裂、细胞分化和迁移以及囊泡运输。在许多细胞中，微管网络呈放射状排列，微管的一端（负端）嵌入靠近细胞核，另一端（正端）探索细胞质空间，在生长和收缩之间不断切换。哺乳动物的正端追踪蛋白（+TIPs）定位于生长中的微管的末端，并调节微管的动态行为以及微管与其他细胞成分的相互作用。由于这些关键作用，+TIPs 及其与微管末端结合的机制受到了广泛的研究。研究结果表明，+TIPs 通过马达介导的运输或扩散到达微管末端。单个+TIP 分子在微管聚合过程中形成的微管末端结合位点上快速交换，这些结合位点的周转率较慢。大多数+TIPs 与末端结合（EB）蛋白结合，并且似乎需要这些“核心”+TIPs 才能定位在微管末端。+TIPs 的积累也可能涉及微管末端的结构特征和与其他+TIPs 的相互作用。这种复杂性使得难以将特定+TIPs 的离散作用分配给它们。鉴于+TIPs 在微管末端聚集，并且每个+TIP 以独特的构象结合，我提出，生长中的微管末端是特定蛋白质之间有效相互作用的“纳米平台”，并且这些相互作用可能在细胞质的其他地方持续存在并且具有功能，而不仅仅在它们起源的微管末端。
