Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Department of Biochemistry and Molecular Biology and the Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, USA.
Neurosci Lett. 2021 Apr 23;751:135806. doi: 10.1016/j.neulet.2021.135806. Epub 2021 Mar 8.
Microtubules are the structural center of neurons, stretching in overlapping arrays from the cell body to the far reaches of axons and dendrites. They also act as the tracks for long-range transport mediated by dynein and kinesin motors. Transcription and most translation take place in the cell body, and newly made cargoes must be shipped from this site of synthesis to sites of function in axons and dendrites. This constant demand for transport means that the microtubule array must be present without gaps throughout the cell over the lifetime of the animal. This task is made slightly easier in many animals by the relatively long, stable microtubules present in neurons. However, even stable neuronal microtubules have ends that are dynamic, and individual microtubules typically last on the order of hours, while the neurons around them last a lifetime. "Birth" of new microtubules is therefore required to maintain the neuronal microtubule array. In this review we discuss the nucleation of new microtubules in axons and dendrites, including how and where they are nucleated. In addition, it is becoming clear that neuronal microtubule nucleation is highly regulated, with unexpected machinery impinging on the decision of whether nucleation sites are active or inactive through space and time.
微管是神经元的结构中心,从细胞体延伸到轴突和树突的远端,呈重叠排列。它们还充当由动力蛋白和驱动蛋白介导的长距离运输的轨道。转录和大多数翻译发生在细胞体中,新合成的货物必须从这个合成部位运输到轴突和树突的功能部位。这种对运输的持续需求意味着,在动物的整个生命周期中,微管阵列必须在整个细胞中无间隙地存在。在许多动物中,由于神经元中存在相对较长且稳定的微管,这个任务稍微容易一些。然而,即使是稳定的神经元微管也有动态的末端,单个微管通常持续数小时,而周围的神经元则持续一生。因此,需要新的微管来维持神经元微管阵列。在这篇综述中,我们讨论了轴突和树突中新微管的成核,包括它们是如何以及在何处成核的。此外,越来越明显的是,神经元微管的成核受到高度调控,通过空间和时间,意想不到的机制影响着成核位点是活跃还是不活跃的决定。