Hanlon D W, Yang Z, Goldstein L S
Department of Pharmacology, University of California, San Diego, La Jolla 92093-0683, USA.
Neuron. 1997 Mar;18(3):439-51. doi: 10.1016/s0896-6273(00)81244-1.
Members of the kinesin superfamily of microtubule-associated proteins are involved in a variety of intracellular processes including cell division and organelle transport. In the case of axonal transport, all kinesin superfamily members reported thus far appear to play a role in anterograde transport, while a different type of microtubule motor, dynein, appears to function in retrograde transport. To better understand the role of kinesins in axonal transport, we cloned and characterized KIFC2, a novel kinesin superfamily member from mouse brain. KIFC2 encodes a 792 amino acid protein, which contains the conserved motor domain at the C-terminal end of the protein and is most similar to members of the KAR3 family involved in cell division. However, expression analysis localized KIFC2 mRNA to nonproliferative neuronal cells in the central nervous system, and immunolocalization studies demonstrated that KIFC2 is present in axons and dendrites of neurons in the central and peripheral nervous systems. Immunolocalization and biochemical fractionation studies suggest that KIFC2 localizes with some, but not all, axonally transported organelles. Finally, ligation of mouse peripheral nerves showed that KIFC2 accumulates at the proximal and distal sides of an axonal ligature. Taken together, the data suggest that, unlike other C-terminal motor proteins that appear to be involved in cell division, KIFC2 may play a role in retrograde axonal transport.
微管相关蛋白的驱动蛋白超家族成员参与多种细胞内过程,包括细胞分裂和细胞器运输。就轴突运输而言,迄今为止报道的所有驱动蛋白超家族成员似乎都在顺行运输中发挥作用,而另一种微管运动蛋白动力蛋白则似乎在逆行运输中发挥作用。为了更好地理解驱动蛋白在轴突运输中的作用,我们克隆并鉴定了KIFC2,它是一种来自小鼠大脑的新型驱动蛋白超家族成员。KIFC2编码一种792个氨基酸的蛋白质,该蛋白质在其C末端含有保守的运动结构域,并且与参与细胞分裂的KAR3家族成员最为相似。然而,表达分析将KIFC2 mRNA定位到中枢神经系统中不增殖的神经元细胞,免疫定位研究表明KIFC2存在于中枢和外周神经系统神经元的轴突和树突中。免疫定位和生化分级分离研究表明,KIFC2与一些但不是所有轴突运输的细胞器共定位。最后,小鼠外周神经结扎显示KIFC2在轴突结扎的近端和远端积累。综上所述,数据表明,与其他似乎参与细胞分裂的C末端运动蛋白不同,KIFC2可能在轴突逆行运输中发挥作用。