Dent Erik W
Department of Neuroscience, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53705
Mol Biol Cell. 2017 Jan 1;28(1):1-8. doi: 10.1091/mbc.E15-11-0769.
Microtubules (MTs) are cytoskeletal polymers composed of repeating subunits of tubulin that are ubiquitously expressed in eukaryotic cells. They undergo a stochastic process of polymerization and depolymerization from their plus ends termed dynamic instability. MT dynamics is an ongoing process in all cell types and has been the target for the development of several useful anticancer drugs, which compromise rapidly dividing cells. Recent studies also suggest that MT dynamics may be particularly important in neurons, which develop a highly polarized morphology, consisting of a single axon and multiple dendrites that persist throughout adulthood. MTs are especially dynamic in dendrites and have recently been shown to polymerize directly into dendritic spines, the postsynaptic compartment of excitatory neurons in the CNS. These transient polymerization events into dendritic spines have been demonstrated to play important roles in synaptic plasticity in cultured neurons. Recent studies also suggest that MT dynamics in the adult brain function in the essential process of learning and memory and may be compromised in degenerative diseases, such as Alzheimer's disease. This raises the possibility of targeting MT dynamics in the design of new therapeutic agents.
微管(MTs)是由微管蛋白的重复亚基组成的细胞骨架聚合物,在真核细胞中普遍表达。它们从其正端经历一个随机的聚合和解聚过程,称为动态不稳定性。微管动力学在所有细胞类型中都是一个持续的过程,并且一直是几种有用的抗癌药物开发的靶点,这些药物会损害快速分裂的细胞。最近的研究还表明,微管动力学在神经元中可能特别重要,神经元会发育出高度极化的形态,由一条单一的轴突和多个贯穿成年期的树突组成。微管在树突中尤其具有动态性,最近已被证明可以直接聚合成树突棘,即中枢神经系统中兴奋性神经元的突触后区室。这些进入树突棘的短暂聚合事件已被证明在培养神经元的突触可塑性中起重要作用。最近的研究还表明,成人大脑中的微管动力学在学习和记忆的基本过程中发挥作用,并且在诸如阿尔茨海默病等退行性疾病中可能会受到损害。这增加了在设计新治疗药物时靶向微管动力学的可能性。