title: Hikeshi, a nuclear import carrier for Hsp70s, protects cells from heat shock-induced nuclear damage.
abstract: During heat shock stress, importin β family-mediated nucleocytoplasmic trafficking is downregulated, whereas nuclear import of the molecular chaperone Hsp70s is upregulated. Here, we identify a nuclear import pathway that operates during heat shock stress and is mediated by an evolutionarily conserved protein named "Hikeshi," which does not belong to the importin β family. Hikeshi binds to FG-Nups and translocates through nuclear pores on its own, showing characteristic features of nuclear transport carriers. In reconstituted transport, Hikeshi supports the nuclear import of the ATP form of Hsp70s, but not the ADP form, indicating the importance of the Hsp70 ATPase cycle in the import cycle. In living cells, depletion of Hikeshi inhibits heat shock-induced nuclear import of Hsp70s, reduces cell viability after heat shock stress, and significantly delays the attenuation and reversion of multiple heat shock-induced nuclear phenotypes. Nuclear Hsp70s rescue the effect of Hikeshi depletion at least in part. Thus, Hsp70s counteract heat shock-induced damage by acting inside of the nucleus.
authors.affiliation: Cellular Dynamics Laboratory, RIKEN Advanced Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. skose@riken.jp
authors.forename: Shingo
authors.initials: S
authors.lastname: Kose
authors.forename: Maiko
authors.initials: M
authors.lastname: Furuta
authors.forename: Naoko
authors.initials: N
authors.lastname: Imamoto
mesh_terms: D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006367:HeLa Cells; D018869:Heat-Shock Response; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism; D008969:Molecular Sequence Data; D022022:Nuclear Pore / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D002352:Carrier Proteins; D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones; C572913:hikeshi protein, human