Hirokawa Nobutaka, Takemura Reiko
Department of Cell Biology and Anatomy, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
Exp Cell Res. 2004 Nov 15;301(1):50-9. doi: 10.1016/j.yexcr.2004.08.010.
Kinesin superfamily proteins (KIFs) are motor proteins that transport membranous organelles and macromolecules fundamental for cellular functions along microtubules. Their roles in transport in axons and dendrites have been studied extensively, but KIFs are also used in intracellular transport in general. Recent findings have revealed that in many cases, the specific interaction of cargoes and motors is mediated via adaptor/scaffolding proteins. Cargoes are sorted to precise destinations, such as axons or dendrites. KIFs also participate in polarized transport in epithelial cells as shown in the apical transport of annexin XIIIb-containing vesicles by KIFC3. KIFs play important roles in higher order neuronal activity; transgenic mice overexpressing KIF17, which transports N-methyl-d-asp (NMDA) receptors to dendrites, show enhanced memory and learning. KIFs also play significant roles in neuronal development and brain wiring: KIF2A suppresses elongation of axon collaterals by its unique microtubule-depolymerizing activity. X-ray crystallography has revealed the structural uniqueness of KIF2 underlying the microtubule-depolymerizing activity. In addition, single molecule biophysics and optical trapping have shown that the motility of monomeric KIF1A is caused by biased Brownian movement, and X-ray crystallography has shown how the conformational changes occur for KIF1A to move during ATP hydrolysis. These multiple approaches in analyzing KIF functions will illuminate many basic mechanisms underlying intracellular events and will be a very promising and fruitful area for future studies.
驱动蛋白超家族蛋白（KIFs）是一类运动蛋白，可沿微管运输对细胞功能至关重要的膜性细胞器和大分子。它们在轴突和树突运输中的作用已得到广泛研究，但KIFs通常也用于细胞内运输。最近的研究发现，在许多情况下，货物与马达的特异性相互作用是通过衔接蛋白/支架蛋白介导的。货物被分选到精确的目的地，如轴突或树突。如KIFC3介导含膜联蛋白XIIIb的囊泡向顶端运输所示，KIFs也参与上皮细胞的极性运输。KIFs在更高层次的神经元活动中发挥重要作用；过表达将N-甲基-D-天冬氨酸（NMDA）受体运输到树突的KIF17的转基因小鼠表现出增强的记忆和学习能力。KIFs在神经元发育和脑布线中也发挥着重要作用：KIF2A通过其独特的微管解聚活性抑制轴突侧支的伸长。X射线晶体学揭示了KIF2微管解聚活性背后的结构独特性。此外，单分子生物物理学和光镊技术表明，单体KIF1A的运动是由偏向布朗运动引起的，X射线晶体学展示了KIF1A在ATP水解过程中发生构象变化以实现移动的方式。这些分析KIF功能的多种方法将阐明细胞内事件背后的许多基本机制，并将成为未来研究中一个非常有前景且富有成果的领域。
