Laboratory of Musculoskeletal Cell Biology, Rizzoli Orthopedic Institute, Bologna, Italy.
J Cell Biochem. 2011 Apr;112(4):979-92. doi: 10.1002/jcb.22992.
Laminopathies are genetic diseases due to mutations or altered post-translational processing of nuclear envelope/lamina proteins. The majority of laminopathies are caused by mutations in the LMNA gene, encoding lamin A/C, but manifest as diverse pathologies including muscular dystrophy, lipodystrophy, neuropathy, and progeroid syndromes. Lamin-binding proteins implicated in laminopathies include lamin B2, nuclear envelope proteins such as emerin, MAN1, LBR, and nesprins, the nuclear matrix protein matrin 3, the lamina-associated polypeptide, LAP2alpha and the transcriptional regulator FHL1. Thus, the altered functionality of a nuclear proteins network appears to be involved in the onset of laminopathic diseases. The functional interplay among different proteins involved in this network implies signaling partners. The signaling effectors may either modify nuclear envelope proteins and their binding properties, or use nuclear envelope/lamina proteins as platforms to regulate signal transduction. In this review, both aspects of lamin-linked signaling are presented and the major pathways so far implicated in laminopathies are summarized.
核纤层病是由核膜/核纤层蛋白基因突变或翻译后修饰改变引起的遗传疾病。大多数核纤层病是由编码核纤层蛋白 A/C 的 LMNA 基因突变引起的，但表现为多种病理学改变，包括肌肉营养不良、脂肪营养不良、神经病和早老综合征。在核纤层病中涉及的核纤层结合蛋白包括核纤层蛋白 B2、核膜蛋白如 emerin、MAN1、LBR 和 nesprins、核基质蛋白 matrin 3、核纤层相关多肽 LAP2alpha 和转录调节因子 FHL1。因此，核蛋白网络的功能改变似乎参与了核纤层病的发病。该网络中不同蛋白之间的功能相互作用暗示着信号伙伴的存在。信号效应物可能修饰核膜蛋白及其结合特性，或利用核膜/核纤层蛋白作为平台来调节信号转导。在这篇综述中，介绍了核纤层连接信号的两个方面，并总结了迄今为止与核纤层病相关的主要途径。
