Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, USA.
Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, USA; Department of Radiology, University of North Carolina at Chapel Hill, USA.
Curr Opin Cell Biol. 2023 Dec;85:102266. doi: 10.1016/j.ceb.2023.102266. Epub 2023 Oct 20.
Neurofilaments (NFs) and GFAP are cytoskeletal intermediate filaments (IFs) that support cellular processes unfolding within the uniquely complex environments of neurons and astrocytes, respectively. This review highlights emerging concepts on the transitions between stable and destabilized IF networks in the nervous system. While self-association between transiently structured low-complexity IF domains promotes filament assembly, the opposing destabilizing actions of phosphorylation-mediated filament severing facilitate faster intracellular transport. Cellular proteases, including caspases and calpains, produce a variety of IF fragments, which may interact with N-degron and C-degron pathways of the protein degradation machinery. The rapid adoption of NF and GFAP-based clinical biomarker tests is contrasted with the lagging understanding of the dynamics between the native IF proteins and their fragments.
神经丝(NFs)和 GFAP 是细胞骨架中间丝(IFs),分别支持神经元和星形胶质细胞内独特复杂环境中的细胞过程。本综述强调了神经系统中稳定和不稳定 IF 网络之间转变的新出现概念。虽然瞬时结构的低复杂度 IF 结构域之间的自缔合促进了纤维丝的组装,但磷酸化介导的纤维丝切断的相反去稳定作用促进了更快的细胞内运输。包括半胱天冬酶和钙蛋白酶在内的细胞蛋白酶产生各种 IF 片段,这些片段可能与蛋白降解机制的 N-降解和 C-降解途径相互作用。NF 和 GFAP 为基础的临床生物标志物检测的快速采用与对天然 IF 蛋白及其片段之间动态关系的滞后理解形成对比。