Burke Brian, Stewart Colin L
Nuclear Dynamics and Architecture Group, Institute of Medical Biology, Immunos, Singapore, Singapore.
Development and Regenerative Biology Group, Institute of Medical Biology, Immunos, Singapore, Singapore.
Curr Top Dev Biol. 2014;109:1-52. doi: 10.1016/B978-0-12-397920-9.00006-8.
In eukaryotes, the function of the cell's nucleus has primarily been considered to be the repository for the organism's genome. However, this rather simplistic view is undergoing a major shift, as it is increasingly apparent that the nucleus has functions extending beyond being a mere genome container. Recent findings have revealed that the structural composition of the nucleus changes during development and that many of these components exhibit cell- and tissue-specific differences. Increasing evidence is pointing to the nucleus being integral to the function of the interphase cytoskeleton, with changes to nuclear structural proteins having ramifications affecting cytoskeletal organization and the cell's interactions with the extracellular environment. Many of these functions originate at the nuclear periphery, comprising the nuclear envelope (NE) and underlying lamina. Together, they may act as a "hub" in integrating cellular functions including chromatin organization, transcriptional regulation, mechanosignaling, cytoskeletal organization, and signaling pathways. Interest in such an integral role has been largely stimulated by the discovery that many diseases and anomalies are caused by defects in proteins of the NE/lamina, the nuclear envelopathies, many of which, though rare, are providing insights into their more common variants that are some of the major issues of the twenty-first century public health. Here, we review the contributions that mouse mutants have made to our current understanding of the NE/lamina, their respective roles in disease and the use of mice in developing potential therapies for treating the diseases.
在真核生物中，细胞核的功能主要被认为是生物体基因组的储存库。然而，这种相当简单化的观点正在经历重大转变，因为越来越明显的是，细胞核的功能不仅限于仅仅作为基因组的容器。最近的研究发现表明，细胞核的结构组成在发育过程中会发生变化，而且其中许多成分表现出细胞和组织特异性差异。越来越多的证据表明，细胞核对于间期细胞骨架的功能至关重要，核结构蛋白的变化会对细胞骨架组织以及细胞与细胞外环境的相互作用产生影响。这些功能中的许多都起源于核周区域，包括核膜（NE）和其下方的核纤层。它们共同作用，可能作为一个“枢纽”来整合细胞功能，包括染色质组织、转录调控、机械信号传导、细胞骨架组织和信号通路。对这种不可或缺作用的兴趣很大程度上是由以下发现所激发的：许多疾病和异常是由核膜/核纤层蛋白缺陷引起的，即核膜病，其中许多虽然罕见，但却为了解二十一世纪公共卫生的一些主要问题——更常见的变体提供了线索。在这里，我们回顾了小鼠突变体对我们目前对核膜/核纤层的理解所做的贡献、它们在疾病中的各自作用以及利用小鼠开发治疗这些疾病的潜在疗法。
