Cartwright Sarah, Karakesisoglou Iakowos
School of Biological and Biomedical Sciences, University of Durham, Durham DH1 3LE, UK.
School of Biological and Biomedical Sciences, University of Durham, Durham DH1 3LE, UK.
Semin Cell Dev Biol. 2014 May;29:169-79. doi: 10.1016/j.semcdb.2013.12.010. Epub 2013 Dec 25.
LINC (Linker of Nucleoskeleton and Cytoskeleton) complex is an evolutionary conserved structure that spans the entire nuclear envelope (NE), and integrates the nuclear interior with the cytoskeleton, in order to support a diverse array of fundamental biological processes. Key components of the LINC complex are the nesprins (Nuclear Envelope SPectrin Repeat proteINS) that were initially described as large integral NE proteins. However, nesprin genes are complex and generate many variants, which occupy various sub-cellular compartments suggesting additional functions. Hence, the potential involvement of nesprins in disease has expanded immensely on what we already know. That is, nesprins are implicated in diseases such as cancer, myopathies, arthrogryposis, neurological disorders and hearing loss. Here we review nesprins by providing an in depth account of their structure, molecular interactions and cellular functions with relevance to their potential roles in disease. Specifically, we speculate about possible pathomechanisms underlying nesprin-associated diseases.
LINC（核骨架与细胞骨架连接体）复合体是一种进化上保守的结构，它横跨整个核膜（NE），并将细胞核内部与细胞骨架整合在一起，以支持一系列基本的生物学过程。LINC复合体的关键组成部分是核纤层蛋白（Nuclear Envelope SPectrin Repeat proteINS），最初被描述为大型整合核膜蛋白。然而，核纤层蛋白基因很复杂，会产生许多变体，这些变体占据了各种亚细胞区室，表明它们具有其他功能。因此，核纤层蛋白在疾病中的潜在作用比我们已知的要广泛得多。也就是说，核纤层蛋白与癌症、肌病、关节挛缩、神经疾病和听力损失等疾病有关。在这里，我们通过深入阐述核纤层蛋白的结构、分子相互作用和细胞功能，以及它们在疾病中的潜在作用，对核纤层蛋白进行综述。具体来说，我们推测了核纤层蛋白相关疾病潜在的发病机制。
