Article

  • The EMBO Journal (2005) 24, 942 - 951
  • doi:10.1038/sj.emboj.7600587

Published online: 17 February 2005

Importin alpha transports CaMKIV to the nucleus without utilizing importin bold beta

Ippei Kotera1, Toshihiro Sekimoto1, Yoichi Miyamoto2, Takuya Saiwaki1, Emi Nagoshi1, Hiroyuki Sakagami3, Hisatake Kondo3 and Yoshihiro Yoneda1,2

  1. Department of Cell Biology and Neuroscience, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
  2. Department of Frontier Biosciences, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka, Japan
  3. Department of Cell Biology, Graduate School of Medicine, Tohoku University, Aoba-ku, Sendai, Japan

Correspondence to:

Yoshihiro Yoneda, Department of Frontier Biosciences, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan. Tel.: +81 6 6879 4606; Fax: +81 6 6879 4609; E-mail: yyoneda@anat3.med.osaka-u.ac.jp

Received 22 November 2004; Accepted 27 January 2005


Ca2+/calmodulin-dependent protein kinase type IV (CaMKIV) plays an essential role in the transcriptional activation of cAMP response element-binding protein-mediated signaling pathways. Although CaMKIV is localized predominantly in the nucleus, the molecular mechanism of the nuclear import of CaMKIV has not been elucidated. We report here that importin alpha is able to carry CaMKIV into the nucleus without the need for importin beta or any other soluble proteins in digitonin-permeabilized cells. An importin beta binding-deficient mutant (DeltaIBB) of importin alpha also carried CaMKIV into the nucleus, which strongly suggests that CaMKIV is transported in an importin beta-independent manner. While CaMKIV directly interacted with the C-terminal region of importin alpha, the CaMKIV/importin alpha complex did not form a ternary complex with importin beta, which explains the nonrequirement of importin beta for the nuclear transport of CaMKIV. The cytoplasmic microinjection of importin alpha-DeltaIBB enhanced the rate of nuclear translocation of CaMKIV in vivo. This is the first report to demonstrate definitely that mammalian importin alpha solely carries a cargo protein into the nucleus without utilizing the classical importin beta-dependent transport system.

  • Keywords:

    • CaMKIV,
    • importin alpha,
    • importin beta,
    • nuclear transport,
    • Ran
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