1. Biochemistry and Chemical Biology
  2. Cell Biology
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Extensive cargo identification reveals distinct biological roles of the 12 importin pathways

  1. Makoto Kimura  Is a corresponding author
  2. Yuriko Morinaka
  3. Kenichiro Imai
  4. Shingo Kose
  5. Paul Horton
  6. Naoko Imamoto  Is a corresponding author
  1. RIKEN, Japan
  2. National Institute of Advanced Industrial Science and Technology, Japan
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Cite this article as: eLife 2017;6:e21184 doi: 10.7554/eLife.21184

Abstract

Vast numbers of proteins are transported into and out of the nuclei by approximately 20 species of importin-β family nucleocytoplasmic transport receptors. However, the significance of the multiple parallel transport pathways that the receptors constitute is poorly understood because only limited numbers of cargo proteins have been reported. Here, we identified cargo proteins specific to the 12 species of human import receptors with a high-throughput method that employs stable isotope labeling with amino acids in cell culture, an in vitro reconstituted transport system, and quantitative mass spectrometry. The identified cargoes illuminated the manner of cargo allocation to the receptors. The redundancies of the receptors vary widely depending on the cargo protein. Cargoes of the same receptor are functionally related to one another, and the predominant protein groups in the cargo cohorts differ among the receptors. Thus, the receptors are linked to distinct biological processes by the nature of their cargoes.

Article and author information

Author details

  1. Makoto Kimura

    Cellular Dynamics Laboratory, RIKEN, Wako, Japan
    For correspondence
    makimura@riken.jp
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0868-5334
  2. Yuriko Morinaka

    Cellular Dynamics Laboratory, RIKEN, Wako, Japan
    Competing interests
    The authors declare that no competing interests exist.
  3. Kenichiro Imai

    Artificial Intelligence Research Center, National Institute of Advanced Industrial Science and Technology, Tokyo, Japan
    Competing interests
    The authors declare that no competing interests exist.
  4. Shingo Kose

    Cellular Dynamics Laboratory, RIKEN, Wako, Japan
    Competing interests
    The authors declare that no competing interests exist.
  5. Paul Horton

    Artificial Intelligence Research Center, National Institute of Advanced Industrial Science and Technology, Tokyo, Japan
    Competing interests
    The authors declare that no competing interests exist.
  6. Naoko Imamoto

    Cellular Dynamics Laboratory, RIKEN, Wako, Japan
    For correspondence
    nimamoto@riken.jp
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2886-3022

Funding

Japan Society for the Promotion of Science (KAKENHI,15K07064)

  • Makoto Kimura

RIKEN (FY2014 Incentive Research Project)

  • Makoto Kimura

Japan Society for the Promotion of Science (KAKENHI,26251021,26116526,15H05929)

  • Naoko Imamoto

Japan Agency for Medical Research and Development (Platform Project for Supporting in Drug Discovery and Life Science Research)

  • Kenichiro Imai

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Karsten Weis, ETH Zurich, Switzerland

Publication history

  1. Received: September 2, 2016
  2. Accepted: January 17, 2017
  3. Accepted Manuscript published: January 24, 2017 (version 1)
  4. Version of Record published: February 13, 2017 (version 2)

Copyright

© 2017, Kimura et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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