Sobo Joan M, Alagna Nicholas S, Sun Sean X, Wilson Katherine L, Reddy Karen L
Department of Biological Chemistry, Center for Epigenetics, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
Department of Mechanical Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD 21205, USA.
Curr Opin Cell Biol. 2024 Feb;86:102313. doi: 10.1016/j.ceb.2023.102313. Epub 2024 Jan 22.
The nuclear lamina (NL) is a crucial component of the inner nuclear membrane (INM) and consists of lamin filaments and associated proteins. Lamins are type V intermediate filament proteins essential for maintaining the integrity and mechanical properties of the nucleus. In human cells, 'B-type' lamins (lamin B1 and lamin B2) are ubiquitously expressed, while 'A-type' lamins (lamin A, lamin C, and minor isoforms) are expressed in a tissue- and development-specific manner. Lamins homopolymerize to form filaments that localize primarily near the INM, but A-type lamins also localize to and function in the nucleoplasm. Lamins play central roles in the assembly, structure, positioning, and mechanics of the nucleus, modulating cell signaling and influencing development, differentiation, and other activities. This review highlights recent findings on the structure and regulation of lamin filaments, providing insights into their multifaceted functions, including their role as "mechanosensors", delving into the emerging significance of lamin filaments as vital links between cytoskeletal and nuclear structures, chromatin organization, and the genome.
核纤层(NL)是内核膜(INM)的关键组成部分,由核纤层蛋白丝和相关蛋白组成。核纤层蛋白是V型中间丝蛋白,对维持细胞核的完整性和力学性质至关重要。在人类细胞中,“B型”核纤层蛋白(核纤层蛋白B1和核纤层蛋白B2)普遍表达,而“A型”核纤层蛋白(核纤层蛋白A、核纤层蛋白C和次要异构体)则以组织和发育特异性的方式表达。核纤层蛋白通过同聚作用形成主要定位于内核膜附近的丝状物,但A型核纤层蛋白也定位于核质并在其中发挥作用。核纤层蛋白在细胞核的组装、结构、定位和力学方面发挥核心作用,调节细胞信号传导并影响发育、分化和其他活动。本综述重点介绍了核纤层蛋白丝结构和调控方面的最新发现,深入探讨了它们的多方面功能,包括其作为“机械传感器”的作用,探究了核纤层蛋白丝作为细胞骨架与核结构、染色质组织和基因组之间重要联系的新意义。