The Mobile FG Nucleoporin Nup98 Is a Cofactor for Crm1-dependent Protein Export |
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| Authors: | Masahiro Oka Munehiro Asally Yoshinari Yasuda Yutaka Ogawa Taro Tachibana Yoshihiro Yoneda |
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| Affiliation: | *Biomolecular Dynamics Group, Graduate School of Frontier Biosciences.;†Department of Biochemistry, Graduate School of Medicine, Osaka University, and ;‡Japan Science and Technology Corporation (JST), Core Research for Evolution Science and Technology (CREST), Osaka University, Suita, Osaka 565-0871, Japan; and ;§Department of Bioengineering, Graduate School of Engineering, Osaka City University, Osaka 558-8585, Japan |
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| Abstract: | Nup98 is a mobile nucleoporin that forms distinct dots in the nucleus, and, although a role for Nup98 in nuclear transport has been suggested, its precise function remains unclear. Here, we show that Nup98 plays an important role in Crm1-mediated nuclear protein export. Nuclear, but not cytoplasmic, dots of EGFP-tagged Nup98 disappeared rapidly after cell treatment with leptomycin B, a specific inhibitor of the nuclear export receptor, Crm1. Mutational analysis demonstrated that Nup98 physically and functionally interacts with Crm1 in a RanGTP-dependent manner through its N-terminal phenylalanine-glycine (FG) repeat region. Moreover, the activity of the Nup98-Crm1 complex was modulated by RanBP3, a known cofactor for Crm1-mediated nuclear export. Finally, cytoplasmic microinjection of anti-Nup98 inhibited the Crm1-dependent nuclear export of proteins, concomitant with the accumulation of anti-Nup98 in the nucleus. These results clearly demonstrate that Nup98 functions as a novel shuttling cofactor for Crm1-mediated nuclear export in conjunction with RanBP3. |
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