Kondo S, Sato-Yoshitake R, Noda Y, Aizawa H, Nakata T, Matsuura Y, Hirokawa N
Department of Anatomy and Cell Biology, School of Medicine, University of Tokyo, Japan.
J Cell Biol. 1994 Jun;125(5):1095-107. doi: 10.1083/jcb.125.5.1095.
Neurons are highly polarized cells composed of dendrites, cell bodies, and long axons. Because of the lack of protein synthesis machinery in axons, materials required in axons and synapses have to be transported down the axons after synthesis in the cell body. Fast anterograde transport conveys different kinds of membranous organelles such as mitochondria and precursors of synaptic vesicles and axonal membranes, while organelles such as endosomes and autophagic prelysosomal organelles are conveyed retrogradely. Although kinesin and dynein have been identified as good candidates for microtubule-based anterograde and retrograde transporters, respectively, the existence of other motors for performing these complex axonal transports seems quite likely. Here we characterized a new member of the kinesin super-family, KIF3A (50-nm rod with globular head and tail), and found that it is localized in neurons, associated with membrane organelle fractions, and accumulates with anterogradely moving membrane organelles after ligation of peripheral nerves. Furthermore, native KIF3A (a complex of 80/85 KIF3A heavy chain and a 95-kD polypeptide) revealed microtubule gliding activity and baculovirus-expressed KIF3A heavy chain demonstrated microtubule plus end-directed (anterograde) motility in vitro. These findings strongly suggest that KIF3A is a new motor protein for the anterograde fast axonal transport.
神经元是由树突、细胞体和长轴突组成的高度极化细胞。由于轴突中缺乏蛋白质合成机制,轴突和突触所需的物质必须在细胞体中合成后沿轴突运输。快速顺向运输传递各种膜性细胞器,如线粒体、突触小泡前体和轴突膜,而内体和自噬前溶酶体细胞器等则逆向运输。尽管驱动蛋白和动力蛋白已分别被确认为基于微管的顺向和逆向转运体的良好候选者,但很可能还存在其他执行这些复杂轴突运输的马达蛋白。在这里,我们鉴定了驱动蛋白超家族的一个新成员KIF3A(具有球状头部和尾部的50纳米杆状结构),发现它定位于神经元中,与膜细胞器部分相关,并且在结扎外周神经后与顺向移动的膜细胞器聚集在一起。此外,天然KIF3A(80/85 KIF3A重链和95-kD多肽的复合物)显示出微管滑动活性,并且杆状病毒表达的KIF3A重链在体外表现出微管正端定向(顺向)运动。这些发现强烈表明KIF3A是顺向快速轴突运输的一种新的马达蛋白。