Klymkowsky Michael W
Molecular, Cellular & Developmental Biology, University of Colorado, Boulder, Boulder, CO, 80303, USA.
F1000Res. 2019 Sep 30;8. doi: 10.12688/f1000research.19950.1. eCollection 2019.
Cytoplasmic intermediate filaments (IFs) surround the nucleus and are often anchored at membrane sites to form effectively transcellular networks. Mutations in IF proteins (IFps) have revealed mechanical roles in epidermis, muscle, liver, and neurons. At the same time, there have been phenotypic surprises, illustrated by the ability to generate viable and fertile mice null for a number of IFp-encoding genes, including vimentin. Yet in humans, the vimentin ( ) gene displays a high probability of intolerance to loss-of-function mutations, indicating an essential role. A number of subtle and not so subtle IF-associated phenotypes have been identified, often linked to mechanical or metabolic stresses, some of which have been found to be ameliorated by the over-expression of molecular chaperones, suggesting that such phenotypes arise from what might be termed "orphan" effects as opposed to the absence of the IF network , an idea originally suggested by Toivola . and Pekny and Lane.
细胞质中间丝（IFs）环绕着细胞核，并且常常锚定在膜位点上，以有效地形成跨细胞网络。中间丝蛋白（IFps）的突变已揭示其在表皮、肌肉、肝脏和神经元中的机械作用。与此同时，也出现了一些表型上的意外情况，例如能够产生多个编码IFp的基因（包括波形蛋白）缺失的存活且可育的小鼠。然而在人类中，波形蛋白（ ）基因对功能丧失突变表现出高度不耐受性，表明其具有重要作用。已经鉴定出许多细微和不那么细微的与中间丝相关的表型，这些表型通常与机械或代谢应激有关，其中一些已发现通过分子伴侣的过表达而得到改善，这表明此类表型源于可能被称为“孤儿”效应，而不是中间丝网络的缺失，这一观点最初由托伊沃拉以及佩克尼和莱恩提出。
