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.

中文翻译：

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Cdc42 GTPase 调节核膜密封和 ER 重塑中的 ESCRT

Rho 家族的小 GTP 酶是二元分子开关，可调节多种过程，包括细胞迁移和定向细胞分裂。已知的 Cdc42 效应蛋白包括参与细胞骨架重塑和激酶依赖性转录诱导的蛋白质，但没有一个参与维持核膜完整性或 ER 形态。维持核膜完整性需要运输所需的内体复合物（ESCRT）蛋白，但它们在此过程中如何调节仍不清楚。在这里，我们通过活细胞成像展示了 ESCRT 蛋白在核膜和内质网裂变位点的新型 Cdc42 定位，并通过 cdc42 突变酵母的遗传分析，揭示了 Cdc42 在核膜和位点调节 ESCRT 蛋白的独特功能ER 小管裂变。我们的研究结果表明 Cdc42 参与核膜密封和 ER 重塑，它调节 ESCRT 分解以维持核膜完整性和正确的 ER 结构。