Webster Brant M, Lusk C Patrick
Yale School of Medicine, New Haven, CT, USA.
Yale School of Medicine, New Haven, CT, USA.
Trends Cell Biol. 2016 Jan;26(1):29-39. doi: 10.1016/j.tcb.2015.08.002. Epub 2015 Oct 1.
The unique biochemical identity of the nuclear envelope confers its capacity to establish a barrier that protects the nuclear compartment and directly contributes to nuclear function. Recent work uncovered quality control mechanisms employing the endosomal sorting complexes required for transport (ESCRT) machinery and a new arm of endoplasmic reticulum-associated protein degradation (ERAD) to counteract the unfolding, damage, or misassembly of nuclear envelope proteins and ensure the integrity of the nuclear envelope membranes. Moreover, cells have the capacity to recognize and triage defective nuclear pore complexes to prevent their inheritance and preserve the longevity of progeny. These mechanisms serve to highlight the diverse strategies used by cells to maintain nuclear compartmentalization; we suggest they mitigate the progression and severity of diseases associated with nuclear envelope malfunction such as the laminopathies.
核膜独特的生化特性赋予其建立屏障的能力，该屏障可保护核区室并直接促进核功能。最近的研究发现了利用转运所需的内体分选复合体（ESCRT）机制以及内质网相关蛋白降解（ERAD）新分支的质量控制机制，以应对核膜蛋白的解折叠、损伤或错误组装，并确保核膜的完整性。此外，细胞有能力识别并分类有缺陷的核孔复合体，以防止其遗传并保持子代的寿命。这些机制凸显了细胞用于维持核区室化的多种策略；我们认为它们减轻了与核膜功能障碍相关疾病（如核纤层蛋白病）的进展和严重程度。
