Hunter A W, Wordeman L
Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA 98195 USA.
J Cell Sci. 2000 Dec;113 Pt 24:4379-89. doi: 10.1242/jcs.113.24.4379.
The interplay between microtubules and microtubule-based motors is fundamental to basic aspects of cellular function, such as the intracellular transport of organelles and alterations in cellular morphology during cell locomotion and division. Motor proteins are unique in that they couple nucleotide hydrolysis to force production that can do work. The force transduction by proteins belonging to the kinesin and dynein superfamilies has been thought only to power movement of these motors along the surface of microtubules; however, a growing body of evidence, both genetic and biochemical, suggests that motors can also directly influence the polymerization dynamics of microtubules. For example, at the vertebrate kinetochore, motors interact directly with microtubule ends and modulate polymerization dynamics to orchestrate chromosome movements during mitosis. Although a role for motors in regulating microtubule length has been established, the mechanisms used by motors to promote microtubule growth or shrinkage are unclear, as is an understanding of why cells might choose motors to control dynamics rather than a variety of non-motor proteins known to affect microtubule stability. Elucidation of the exact mechanisms by which motors alter the exchange of tubulin subunits at microtubule ends in vitro may shed light on how microtubule stability is regulated to produce the array of dynamic behavior seen in cells.
微管与基于微管的马达蛋白之间的相互作用是细胞功能基本方面的基础，比如细胞器的细胞内运输以及细胞移动和分裂过程中细胞形态的改变。马达蛋白的独特之处在于它们将核苷酸水解与能够做功的力的产生相耦合。人们一直认为，属于驱动蛋白和动力蛋白超家族的蛋白质所进行的力转导仅为这些马达蛋白沿着微管表面的移动提供动力；然而，越来越多的遗传学和生物化学证据表明，马达蛋白也能直接影响微管的聚合动力学。例如，在脊椎动物的动粒处，马达蛋白直接与微管末端相互作用，并调节聚合动力学，以在有丝分裂过程中协调染色体的移动。尽管已经确定了马达蛋白在调节微管长度方面的作用，但马达蛋白促进微管生长或收缩所采用的机制尚不清楚，同样不清楚的是，细胞为何选择马达蛋白来控制动力学，而不是选择各种已知会影响微管稳定性的非马达蛋白。阐明马达蛋白在体外改变微管末端微管蛋白亚基交换的确切机制，可能会揭示微管稳定性是如何被调节以产生细胞中所见的一系列动态行为的。
