Extensive cargo identification reveals distinct biological roles of the 12 importin pathways
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.
Data availability
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SILAC-Tp (12 importins)Publicly available at the Pride Archive (accession no: PXD004655).
Article and author information
Author details
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.
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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