Abstract：
The subcellular compartmentalisation of eukaryotic cells requires selective exchange between the cytoplasm and the nucleus. Intact nucleocytoplasmic transport is vital for normal cell function and mutations in the executing machinery have been causally linked to human disease. Central players in nucleocytoplasmic exchange are nuclear pore complexes (NPCs), which are built from ~30 distinct proteins collectively termed nucleoporins. Aberrant nucleoporin expression was detected in human cancers and autoimmune diseases since quite some time, while it was through the increasing use of next generation sequencing that mutations in nucleoporin genes associated with mainly rare hereditary diseases were revealed. The number of newly identified mutations is steadily increasing, as is the number of diseases. Mutational hotspots have emerged: mutations in the scaffold nucleoporins seemingly affect primarily inner organs, such as heart, kidney, and ovaries, whereas genetic alterations in peripheral, cytoplasmic nucleoporins affect primarily the central nervous system and development. In this review, we summarise latest insights on altered nucleoporin function in the context of human hereditary disorders, with a focus on those where mechanistic insights are beginning to emerge.
摘要：
真核细胞的亚细胞区室化需要细胞质和细胞核之间的选择性交换。完整的核质运输对于正常的细胞功能至关重要，并且执行机制中的突变与人类疾病有因果关系。核质交换的中心参与者是核孔复合物（NPC），它们由大约30种不同的蛋白质组成，统称为核孔蛋白。在人类癌症和自身免疫性疾病中检测到异常的核孔蛋白表达，虽然通过越来越多的使用下一代测序，发现了与主要罕见遗传性疾病相关的核孔蛋白基因的突变。新发现的突变数量正在稳步增加，疾病的数量也是如此。突变热点已经出现：支架核孔蛋白中的突变似乎主要影响内部器官，如心，肾,和卵巢,而外周的遗传改变，细胞质核孔蛋白主要影响中枢神经系统和发育。在这次审查中,我们总结了人类遗传性疾病背景下核孔蛋白功能改变的最新见解，重点是那些机械见解开始出现的地方。
