The Laboratory of Molecular and Cellular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, 8 Center Drive, Bethesda MD 20892, USA.
Dev Biol. 2012 May 15;365(2):445-57. doi: 10.1016/j.ydbio.2012.02.036. Epub 2012 Mar 8.
Nuclear pore complexes (NPCs) are large macromolecular structures embedded in the nuclear envelope (NE), where they facilitate exchange of molecules between the cytoplasm and the nucleoplasm. In most cell types, NPCs are evenly distributed around the NE. However, the mechanisms dictating NPC distribution are largely unknown. Here, we used the model organism Caenorhabditis elegans to identify genes that affect NPC distribution during early embryonic divisions. We found that down-regulation of the Sm proteins, which are core components of the spliceosome, but not down-regulation of other splicing factors, led to clustering of NPCs. Down-regulation of Sm proteins also led to incomplete disassembly of NPCs during mitosis, but had no effect on lamina disassembly, suggesting that the defect in NPC disassembly was not due to a general defect in nuclear envelope breakdown. We further found that these mitotic NPC remnants persisted on an ER membrane that juxtaposes the mitotic spindle. At the end of mitosis, the remnant NPCs moved toward the chromatin and the reforming NE, where they ultimately clustered by forming membrane stacks perforated by NPCs. Our results suggest a novel, splicing-independent, role for Sm proteins in NPC disassembly, and point to a possible link between NPC disassembly in mitosis and NPC distribution in the subsequent interphase.
核孔复合体（NPCs）是嵌入核膜（NE）中的大型大分子结构，它们促进细胞质和核质之间分子的交换。在大多数细胞类型中，NPC 均匀分布在 NE 周围。然而，决定 NPC 分布的机制在很大程度上是未知的。在这里，我们使用模式生物秀丽隐杆线虫来鉴定影响早期胚胎分裂期间 NPC 分布的基因。我们发现，剪接体核心成分 Sm 蛋白的下调，而不是其他剪接因子的下调，导致 NPC 聚集。Sm 蛋白的下调也导致 NPC 在有丝分裂期间不完全解体，但对核层解体没有影响，这表明 NPC 解体的缺陷不是由于核膜破裂的一般缺陷。我们进一步发现，这些有丝分裂 NPC 残余物存在于与有丝分裂纺锤体相邻的内质网膜上。在有丝分裂末期，残余的 NPC 向正在形成的核膜和核质移动，最终通过 NPC 穿孔形成膜堆而聚集。我们的结果表明 Sm 蛋白在 NPC 解体中具有一种新的、与剪接无关的作用，并指出有丝分裂中 NPC 解体与随后的间期 NPC 分布之间可能存在联系。
