期刊
EMBO JOURNAL
卷 40, 期 23, 页码 -出版社
WILEY
DOI: 10.15252/embj.2021108788
关键词
mitotic exit; nuclear pore complex assembly; Nup50; RCC1; Xenopus egg extracts
资金
- German Research Foundation [AN377/7-1]
- Swiss National Science Foundation [310030_184801]
- Swiss National Science Foundation (SNF) [310030_184801] Funding Source: Swiss National Science Foundation (SNF)
Nup50 plays a crucial role in NPC assembly independent of its nuclear transport function. It interacts with Nup153 and MEL28/ELYS through a conserved central region, and its N-terminal fragment stimulates the Ran GTPase guanine nucleotide exchange factor RCC1 to facilitate NPC assembly at the end of mitosis.
During mitotic exit, thousands of nuclear pore complexes (NPCs) assemble concomitant with the nuclear envelope to build a transport-competent nucleus. Here, we show that Nup50 plays a crucial role in NPC assembly independent of its well-established function in nuclear transport. RNAi-mediated downregulation in cells or immunodepletion of Nup50 protein in Xenopus egg extracts interferes with NPC assembly. We define a conserved central region of 46 residues in Nup50 that is crucial for Nup153 and MEL28/ELYS binding, and for NPC interaction. Surprisingly, neither NPC interaction nor binding of Nup50 to importin alpha/beta, the GTPase Ran, or chromatin is crucial for its function in the assembly process. Instead, an N-terminal fragment of Nup50 can stimulate the Ran GTPase guanine nucleotide exchange factor RCC1 and NPC assembly, indicating that Nup50 acts via the Ran system in NPC reformation at the end of mitosis. In support of this conclusion, Nup50 mutants defective in RCC1 binding and stimulation cannot replace the wild-type protein in in vitro NPC assembly assays, whereas excess RCC1 can compensate the loss of Nup50.
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