The nuclear lamina in health and disease.
The nuclear lamina in health and disease.
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DOI：
10.1080/19491034.2016.1183848
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发表时间：
2016-05-03
期刊：
影响因子：
--
通讯作者：
Askjaer P
中科院分区：
文献类型：
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作者：
Dobrzynska A;Gonzalo S;Shanahan C;Askjaer P
核纤层（NL）是核膜的结构组成部分，与核膜蛋白和染色质广泛接触。这些相互作用对于许多细胞过程至关重要，例如核定位、从细胞表面感知机械刺激、核稳定性、染色质的三维组织和染色质结合蛋白（包括转录因子）的调节。NL存在于所有有核后生动物细胞中，但其组成和相互作用组在组织之间不同。最有可能的是，这导致了人类中具有NL相关基因突变的广泛疾病表现，范围从肌肉营养不良到神经系统疾病、脂肪营养不良和早衰综合征。在这里，我们回顾了令人兴奋的新见解NL功能在细胞水平上，特别是在染色质组织和mechanosensation。我们还提出了最近的观察NL和代谢之间的关系和NL在肌肉组织中的特殊相关性。最后，我们讨论了新的治疗方法来治疗NL相关疾病。
The nuclear lamina (NL) is a structural component of the nuclear envelope and makes extensive contacts with integral nuclear membrane proteins and chromatin. These interactions are critical for many cellular processes, such as nuclear positioning, perception of mechanical stimuli from the cell surface, nuclear stability, 3-dimensional organization of chromatin and regulation of chromatin-binding proteins, including transcription factors. The NL is present in all nucleated metazoan cells but its composition and interactome differ between tissues. Most likely, this contributes to the broad spectrum of disease manifestations in humans with mutations in NL-related genes, ranging from muscle dystrophies to neurological disorders, lipodystrophies and progeria syndromes. We review here exciting novel insight into NL function at the cellular level, in particular in chromatin organization and mechanosensation. We also present recent observations on the relation between the NL and metabolism and the special relevance of the NL in muscle tissues. Finally, we discuss new therapeutic approaches to treat NL-related diseases.