Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London, WC1N 3BG London, UK.
Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, University College London, WC1N 3BG London, UK.
Trends Biochem Sci. 2015 Oct;40(10):597-610. doi: 10.1016/j.tibs.2015.08.003.
The intracellular transport of organelles, proteins, lipids, and RNA along the axon is essential for neuronal function and survival. This process, called axonal transport, is mediated by two classes of ATP-dependent motors, kinesins, and cytoplasmic dynein, which carry their cargoes along microtubule tracks. Protein kinases regulate axonal transport through direct phosphorylation of motors, adapter proteins, and cargoes, and indirectly through modification of the microtubule network. The misregulation of axonal transport by protein kinases has been implicated in the pathogenesis of several nervous system disorders. Here, we review the role of protein kinases acting directly on axonal transport and discuss how their deregulation affects neuronal function, paving the way for the exploitation of these enzymes as novel drug targets.
细胞器、蛋白质、脂质和 RNA 沿轴突的细胞内运输对神经元的功能和存活至关重要。这个过程称为轴突运输,由两类 ATP 依赖性马达(驱动蛋白和细胞质动力蛋白)介导,它们沿着微管轨道携带货物。蛋白激酶通过直接磷酸化马达、衔接蛋白和货物,以及间接通过修饰微管网络来调节轴突运输。蛋白激酶对轴突运输的调节失常与几种神经系统疾病的发病机制有关。在这里,我们综述了直接作用于轴突运输的蛋白激酶的作用,并讨论了它们的失调如何影响神经元功能,为这些酶作为新型药物靶点的开发铺平了道路。