Department of Cell Biology, University of Virginia, Charlottesville, Virginia.
Cytoskeleton (Hoboken). 2020 Mar;77(3-4):110-128. doi: 10.1002/cm.21597. Epub 2020 Feb 17.
Neuronal development relies on a highly choreographed progression of dynamic cellular processes by which newborn neurons migrate, extend axons and dendrites, innervate their targets, and make functional synapses. Many of these dynamic processes require coordinated changes in morphology, powered by the cell's cytoskeleton. Intermediate filaments (IFs) are the third major cytoskeletal elements in vertebrate cells, but are rarely considered when it comes to understanding axon and dendrite growth, pathfinding and synapse formation. In this review, we first introduce the many new and exciting concepts of IF function, discovered mostly in non-neuronal cells. These roles include dynamic rearrangements, crosstalk with microtubules and actin filaments, mechano-sensing and -transduction, and regulation of signaling cascades. We then discuss the understudied roles of neuronally expressed IFs, with a particular focus on IFs expressed during development, such as nestin, vimentin and α-internexin. Lastly, we illustrate how signaling modulation by the unconventional IF nestin shapes neuronal morphogenesis in unexpected and novel ways. Even though the first IF knockout mice were made over 20 years ago, the study of the cell biological functions of IFs in the brain still has much room for exciting new discoveries.
神经元的发育依赖于一系列高度协调的动态细胞过程，新生成的神经元通过这些过程迁移、延伸轴突和树突、支配其靶标并形成功能性突触。这些动态过程中的许多都需要细胞骨架协调改变形态，中间丝（IFs）是脊椎动物细胞中的第三大细胞骨架元件，但在理解轴突和树突生长、导向和突触形成时很少被考虑。在这篇综述中，我们首先介绍了 IF 功能的许多新的和令人兴奋的概念，这些概念主要是在非神经元细胞中发现的。这些作用包括动态重排、与微管和肌动蛋白丝的串扰、机械感应和转导，以及信号级联的调节。然后，我们讨论了神经元表达的 IF 研究不足的作用，特别关注在发育过程中表达的 IF，如巢蛋白、波形蛋白和α-中间丝蛋白。最后，我们说明了非典型 IF 巢蛋白如何通过信号转导调节以出人意料和新颖的方式塑造神经元形态发生。尽管第一批 IF 敲除小鼠是在 20 多年前制造的，但 IF 在大脑中的细胞生物学功能的研究仍有很大的空间可以进行令人兴奋的新发现。
