驱动蛋白超家族在多种疾病的发生和发展中的作用  

The role of the kinesin superfamily proteins in the pathogenesis and progression of multiple diseases

作　　者：杨文星 刘鹤 王力 朱元军[3] YANG WenXing LIU He WANG Li ZHU YuanJun(Department of Organismic and Evolutionary Biology, Center for Brain Science, Harvard University, Cambridge MA02138, USA Department of Anesthesiology and Perioperative Medicine, University of Texas MD Anderson Cancer Center, Houston TX77030, USA Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University. Beijing 100191. China)

机构地区：[1]Department of Organismic and Evolutionary Biology, Center for Brain Science, Harvard University [2]Department of Anesthesiology and Perioperative Medicine, University of Texas MD Anderson Cancer Center [3]北京大学药学院分子与细胞药理学系,北京100191

出　　处：《科学通报》2017年第11期1145-1152,共8页Chinese Science Bulletin

基　　金：国家自然科学基金(81302763);北京市自然科学基金(7144218)资助

摘　　要：细胞内物质运输是细胞发挥正常生物学功能的基础.驱动蛋白可作为运送细胞内物质的载体,通过与不同的骨架蛋白结合以识别不同的分子货物,从而参与这些分子货物下游的生物学效应.没有运输活性的驱动蛋白也可以通过其自身对某些分子信号通路的调节而发挥其功能.大量研究表明,驱动蛋白广泛地参与了多种疾病的发生发展过程,如神经性疾病、代谢性疾病、肾病、癌症等.本文将对近年来诸多关于驱动蛋白与疾病的研究进行综述.Intracellular transportation serves as the basis of various cell functions. As the molecular motors responsible for the intracellular transportation, kinesin superfamily proteins（KIFs） recognize diverse molecular cargos, such as proteins, organelles, synaptic vesicles, and RNA granules, via their unique binding structures. KIFs have motor domain, which usually convey ATPase activity. KIFs gain energy from ATP hydrolysis, and transport their cargos moving along the microtubules, thus play important role in biological processes of those cargos. KIFs can be divided into 3 classes, according to the motor domain location on the N-terminal, the C-terminal or the middle of the proteins. Meanwhile, some KIFs lack motor function, which can still play important roles by regulating certain molecular pathways, through their binding proteins. Abundant evidence has shown that the KIFs are widely involved in the pathogenesis and progression of many diseases, such as neuronal diseases, metabolic diseases, kidney diseases, etc. In the present review, we summarize recent research findings which explore the relationship between the KIFs and the diseases. Amyloid ？ peptides（A？） drives Alzheimer’s disease and is derived from the amyloid precursor protein（APP）. APP is transported by binding with KIF5 through c-Jun N-terminal kinase-interacting protein 1（JIP1） and kinesin light chain（KLC） in the axons. APP can also function as a receptor for the transportation of ？-secretase（BACE1） and PS1. Thus, the dysfunction of KIF5 may impair the axonal transport of APP, induce the accumulation of A？, lead to Alzheimer’s disease. Huntingtin mutation can suppress the fast axonal transport by activating axonal c-Jun N-terminal kinase（JNK）. Huntingtin-associated protein 1（HAP1） is enriched in the neurons, which directly binds with KLC in vitro, and colocalizes with KLC in growth cones of the neurons. Knocking down HAP1 suppresses neurite outgrowth of PC12 cells, and inhibits the kinesin-dependent transport

关 键 词：驱动蛋白 细胞内物质运输 KIF 分子马达 微管 

分 类 号：R3411[医药卫生—基础医学]