Department of Chemistry and Ilse Katz Institute for Nanoscale Science and Technology, Ben-Gurion University of the Negev, PO Box 653, 84105, Beer-Sheva, Israel.
Department of Molecular and Cellular Biology, University of California, Davis, Davis, CA, 95616, USA.
Cell Mol Life Sci. 2018 May;75(10):1757-1771. doi: 10.1007/s00018-018-2754-7. Epub 2018 Feb 3.
Mitotic kinesin-5 bipolar motor proteins perform essential functions in mitotic spindle dynamics by crosslinking and sliding antiparallel microtubules (MTs) apart within the mitotic spindle. Two recent studies have indicated that single molecules of Cin8, the Saccharomyces cerevisiae kinesin-5 homolog, are minus end-directed when moving on single MTs, yet switch directionality under certain experimental conditions (Gerson-Gurwitz et al., EMBO J 30:4942-4954, 2011; Roostalu et al., Science 332:94-99, 2011). This finding was unexpected since the Cin8 catalytic motor domain is located at the N-terminus of the protein, and such kinesins have been previously thought to be exclusively plus end-directed. In addition, the essential intracellular functions of kinesin-5 motors in separating spindle poles during mitosis can only be accomplished by plus end-directed motility during antiparallel sliding of the spindle MTs. Thus, the mechanism and possible physiological role of the minus end-directed motility of kinesin-5 motors remain unclear. Experimental and theoretical studies from several laboratories in recent years have identified additional kinesin-5 motors that are bidirectional, revealed structural determinants that regulate directionality, examined the possible mechanisms involved and have proposed physiological roles for the minus end-directed motility of kinesin-5 motors. Here, we summarize our current understanding of the remarkable ability of certain kinesin-5 motors to switch directionality when moving along MTs.
有丝分裂驱动蛋白-5 双极马达蛋白通过交联和滑动有丝分裂纺锤体中的平行微管（MTs）来发挥有丝分裂纺锤体动力学的重要功能。最近的两项研究表明，酿酒酵母驱动蛋白-5 同源物 Cin8 的单个分子在单根 MT 上移动时是负端指向的，但在某些实验条件下会改变方向（Gerson-Gurwitz 等人，《欧洲分子生物学组织杂志》30:4942-4954，2011 年；Roostalu 等人，《科学》332:94-99，2011 年）。这一发现出乎意料，因为 Cin8 的催化马达结构域位于蛋白质的 N 端，而以前认为这种驱动蛋白仅为正端指向。此外，在有丝分裂过程中分离纺锤极的驱动蛋白-5 马达的细胞内基本功能只能通过纺锤 MT 平行滑动时的正端指向运动来完成。因此，驱动蛋白-5 马达的负端指向运动的机制和可能的生理作用仍不清楚。近年来，来自几个实验室的实验和理论研究已经确定了其他的双向驱动蛋白-5 马达，揭示了调节方向的结构决定因素，研究了可能涉及的机制，并提出了驱动蛋白-5 马达的负端指向运动的生理作用。在这里，我们总结了我们目前对某些驱动蛋白-5 马达在沿 MT 运动时改变方向的能力的理解。
