Kuiper E F Elsiena, Prophet Sarah M, Schlieker Christian
Department of Molecular Biophysics & Biochemistry, Yale University, New Haven, CT, USA.
Department of Cell Biology, Yale School of Medicine, New Haven, CT, USA.
FEBS Lett. 2023 Oct;597(20):2534-2545. doi: 10.1002/1873-3468.14725. Epub 2023 Aug 30.
The nuclear pore complex (NPC) is among the most elaborate protein complexes in eukaryotes. While ribosomes and proteasomes are known to require dedicated assembly machinery, our understanding of NPC assembly is at a relatively early stage. Defects in NPC assembly or homeostasis are tied to movement disorders, including dystonia and amyotrophic lateral sclerosis (ALS), as well as aging, requiring a better understanding of these processes to enable therapeutic intervention. Here, we discuss recent progress in the understanding of NPC assembly and highlight how related defects in human disorders can shed light on NPC biogenesis. We propose that the condensation of phenylalanine-glycine repeat nucleoporins needs to be carefully controlled during NPC assembly to prevent aberrant condensation, aggregation, or amyloid formation.
核孔复合体（NPC）是真核生物中最复杂的蛋白质复合体之一。虽然已知核糖体和蛋白酶体需要专门的组装机制，但我们对NPC组装的理解仍处于相对早期阶段。NPC组装或稳态的缺陷与运动障碍有关，包括肌张力障碍和肌萎缩侧索硬化症（ALS），以及衰老，因此需要更好地了解这些过程以实现治疗干预。在这里，我们讨论了在理解NPC组装方面的最新进展，并强调了人类疾病中的相关缺陷如何能够揭示NPC的生物发生。我们提出，在NPC组装过程中，苯丙氨酸-甘氨酸重复核孔蛋白的凝聚需要得到仔细控制，以防止异常凝聚、聚集或淀粉样蛋白形成。
