Department of Cell, The Scripps Research Institute, 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA.
J Struct Biol. 2012 Jan;177(1):24-31. doi: 10.1016/j.jsb.2011.11.007. Epub 2011 Nov 22.
The nuclear lamina is a protein meshwork that lines the nuclear envelope in metazoan cells. It is composed largely of a polymeric assembly of lamins, which comprise a distinct sequence homology class of the intermediate filament protein family. On the basis of its structural properties, the lamina originally was proposed to provide scaffolding for the nuclear envelope and to promote anchoring of chromatin and nuclear pore complexes at the nuclear surface. This viewpoint has expanded greatly during the past 25 years, with a host of surprising new insights on lamina structure, molecular composition and functional attributes. It has been established that the self-assembly properties of lamins are very similar to those of cytoplasmic intermediate filament proteins, and that the lamin polymer is physically associated with components of the cytoplasmic cytoskeleton and with a multitude of chromatin and inner nuclear membrane proteins. Cumulative evidence points to an important role for the lamina in regulating signaling and gene activity, and in mechanically coupling the cytoplasmic cytoskeleton to the nucleus. The significance of the lamina has been vaulted to the forefront by the discovery that mutations in lamins and lamina-associated polypeptides lead to an array of human diseases. A key future challenge is to understand how the lamina integrates pathways for mechanics and signaling at the molecular level. Understanding the structure of the lamina from the atomic to supramolecular levels will be essential for achieving this goal.
核纤层是一种蛋白网格结构，排列在真核细胞的核膜内。它主要由聚合的核纤层蛋白组成，核纤层蛋白属于中间纤维蛋白家族中具有独特序列同源性的一类。根据其结构特性，核纤层最初被认为是为核膜提供支架，并促进染色质和核孔复合物在核表面的锚定。在过去的 25 年中，随着对核纤层结构、分子组成和功能特性的大量新的惊人见解的出现，这种观点已经大大扩展。已经证实，核纤层蛋白的自组装特性与细胞质中间纤维蛋白非常相似，并且核纤层聚合物与细胞质细胞骨架的成分以及大量染色质和内核膜蛋白物理相关。累积的证据表明，核纤层在调节信号转导和基因活性以及机械地将细胞质细胞骨架与细胞核偶联方面发挥着重要作用。核纤层的重要性因发现核纤层蛋白和核纤层相关多肽的突变会导致多种人类疾病而被推到了前沿。未来的一个关键挑战是了解核纤层如何在分子水平上整合力学和信号转导途径。理解核纤层的结构从原子到超分子水平将是实现这一目标的关键。
