Heat-shock stress activates a novel nuclear import pathway mediated by Hikeshi

Abstract

Cellular stresses significantly affect nuclear transport systems. Nuclear transport pathways mediated by importin β-family members, which are active under normal conditions, are downregulated. During thermal stress, a nuclear import pathway mediated by a novel carrier, which we named Hikeshi, becomes active. Hikeshi is not a member of the importin β family and mediates the nuclear import of Hsp70s. Unlike importin β family-mediated nuclear transport, the Hikeshi-mediated nuclear import of Hsp70s is not coupled to the GTPase cycle of the small GTPase Ran but rather is coupled with the ATPase cycle of Hsp70s. Hikeshi-mediated nuclear import is essential for the attenuation and reversal of the thermal stress response in human cells. The mechanism and functions of this newly identified nuclear import pathway will be discussed.

Keywords: :

• nuclear transport
• heat shock stress
• molecular chaperone
• Hsp70
• Importin
• Hikeshi

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Acknowledgments

We thank members of the Cellular Dynamics Lab for helpful comments and discussions. This work was supported by RIKEN Special Funding for Cellular System, ASI FY2012 Fund for Seeds of Collaborative Research to S.K., MEXT grant-in-aids to S.K., and funding awarded to N.I. by the Japan Society for the Promotion of Science (JSPS) through the “Funding Program for Next Generation World-Leading Researchers (NEXT Program),” initiated by the Council for Science and Technology Policy (CSTP).