Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA.
J Cell Biol. 2020 Aug 3;219(8). doi: 10.1083/jcb.201910119.
Small GTPases of the Rho family are binary molecular switches that regulate a variety of processes including cell migration and oriented cell divisions. Known Cdc42 effectors include proteins involved in cytoskeletal remodeling and kinase-dependent transcription induction, but none are involved in the maintenance of nuclear envelope integrity or ER morphology. Maintenance of nuclear envelope integrity requires the EndoSomal Complexes Required for Transport (ESCRT) proteins, but how they are regulated in this process remains unknown. Here, we show by live-cell imaging a novel Cdc42 localization with ESCRT proteins at sites of nuclear envelope and ER fission and, by genetic analysis of cdc42 mutant yeast, uncover a unique Cdc42 function in regulation of ESCRT proteins at the nuclear envelope and sites of ER tubule fission. Our findings implicate Cdc42 in nuclear envelope sealing and ER remodeling, where it regulates ESCRT disassembly to maintain nuclear envelope integrity and proper ER architecture.
Rho 家族的小 GTPases 是二聚体分子开关，调节包括细胞迁移和定向细胞分裂在内的多种过程。已知的 Cdc42 效应物包括参与细胞骨架重塑和激酶依赖性转录诱导的蛋白质，但没有一种涉及核膜完整性或内质网形态的维持。核膜完整性的维持需要内体复合物运输（ESCRT）蛋白，但它们在这个过程中是如何被调节的仍然不清楚。在这里，我们通过活细胞成像显示了一种新的 Cdc42 定位，与 ESCRT 蛋白在核膜和内质网分裂部位的定位，通过对 cdc42 突变酵母的遗传分析，揭示了 Cdc42 在调节核膜和内质网小管分裂部位的 ESCRT 蛋白方面的独特功能。我们的研究结果表明，Cdc42 参与核膜密封和内质网重塑，它调节 ESCRT 解体以维持核膜完整性和内质网结构的适当性。
