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Cellular stresses induce the nuclear accumulation of importin and cause a conventional nuclear import block

¹ Department of Frontier Biosciences, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan
² Department of Biology, Graduate School of Science, Osaka University, Toyonaka, Osaka 560-0043, Japan
³ Core Research for Evolutional Science and Technology of Japan Science and Technology, National Institute for Information and Communications Technology, Nishi-ku, Kobe 651-2492, Japan
⁴ Kansai Advanced Research Center, National Institute for Information and Communications Technology, Nishi-ku, Kobe 651-2492, Japan

Address correspondence to Y. Yoneda, Dept. of Frontier Biosciences, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan. Tel.: 81-6-6879-4605. Fax: 81-6-6879-4609. email: yyoneda{at}anat3.med.osaka-u.ac.jp; or T. Haraguchi, email: tokuko{at}nict.go.jp

We report here that importin accumulates reversibly in the nucleus in response to cellular stresses including UV irradiation, oxidative stress, and heat shock. The nuclear accumulation of importin appears to be triggered by a collapse in the Ran gradient, resulting in the suppression of the nuclear export of importin . In addition, nuclear retention and the importin ß/Ran-independent import of importin also facilitate its rapid nuclear accumulation. The findings herein show that the classical nuclear import pathway is down-regulated via the removal of importin from the cytoplasm in response to stress. Moreover, whereas the nuclear accumulation of heat shock cognate 70 is more sensitive to heat shock than the other stresses, importin is able to accumulate in the nucleus at all the stress conditions tested. These findings suggest that the stress-induced nuclear accumulation of importin can be involved in a common physiological response to various stress conditions.

Key Words: cellular stress; importin/karyopherin; nuclear transport; nuclear localization signal; Ran

Abbreviation used in this paper: hsc, heat shock cognate.

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