A deep proteomics perspective on CRM1-mediated nuclear export and nucleocytoplasmic partitioning

  1. Koray Kırlı
  2. Samir Karaca
  3. Heinz Jürgen Dehne
  4. Matthias Samwer
  5. Kuan Ting Pan
  6. Christof Lenz
  7. Henning Urlaub
  8. Dirk Görlich  Is a corresponding author
  1. Max Planck Institute for Biophysical Chemistry, Germany
  2. Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Austria

Abstract

CRM1 is a highly conserved, RanGTPase-driven exportin that caries proteins and RNPs from the nucleus to the cytoplasm. We now explored the cargo-spectrum of CRM1 in depth and identified surprisingly large numbers, namely >700 export substrates from the yeast S. cerevisiae, ≈ 1000 from Xenopus oocytes and >1050 from human cells. In addition, we quantified the partitioning of ≈5000 unique proteins between nucleus and cytoplasm of Xenopus oocytes. The data suggest new CRM1 functions in spatial control of vesicle coat-assembly, centrosomes, autophagy, peroxisome biogenesis, cytoskeleton, ribosome maturation, translation, mRNA degradation, and more generally in precluding a potentially detrimental action of cytoplasmic pathways within the nuclear interior. There are also numerous new instances where CRM1 appears to act in regulatory circuits. Altogether, our dataset allows unprecedented insights into the nucleocytoplasmic organisation of eukaryotic cells, into the contributions of an exceedingly promiscuous exportin and it provides a new basis for NES prediction.

Article and author information

Author details

  1. Koray Kırlı

    Department of Cellular Logistics, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Samir Karaca

    Department of Cellular Logistics, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Heinz Jürgen Dehne

    Department of Cellular Logistics, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Matthias Samwer

    Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  5. Kuan Ting Pan

    Bioanalytical Mass Spectrometry Group, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Christof Lenz

    Bioanalytical Mass Spectrometry Group, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Henning Urlaub

    Bioanalytical Mass Spectrometry Group, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  8. Dirk Görlich

    Department of Cellular Logistics, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
    For correspondence
    goerlich@mpibpc.mpg.de
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: Our work with Xenopus laevis oocytes has been in accordance with all applicable animal welfare regulations and has been approved by the responsible authority ("Niedersächsisches Landesamt für Verbraucherschutz und Ernährungssicherheit"; file number 33.42502-05/A-005/07).

Reviewing Editor

  1. Karsten Weis, ETH Zürich, Switzerland

Publication history

  1. Received: September 9, 2015
  2. Accepted: December 13, 2015
  3. Accepted Manuscript published: December 17, 2015 (version 1)
  4. Accepted Manuscript updated: January 6, 2016 (version 2)
  5. Accepted Manuscript updated: January 12, 2016 (version 3)
  6. Version of Record published: February 12, 2016 (version 4)

Copyright

© 2015, Kirli 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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  1. Koray Kırlı
  2. Samir Karaca
  3. Heinz Jürgen Dehne
  4. Matthias Samwer
  5. Kuan Ting Pan
  6. Christof Lenz
  7. Henning Urlaub
  8. Dirk Görlich
(2015)
A deep proteomics perspective on CRM1-mediated nuclear export and nucleocytoplasmic partitioning
eLife 4:e11466.
https://doi.org/10.7554/eLife.11466

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    Few studies have assessed the role of individual plasma cholesterol levels in the association between egg consumption and the risk of cardiovascular diseases. This research aims to simultaneously explore the associations of self-reported egg consumption with plasma metabolic markers and these markers with the risk of cardiovascular disease (CVD).

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    Funding:

    This work was supported by the National Natural Science Foundation of China (81973125, 81941018, 91846303, 91843302). The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up is supported by grants (2016YFC0900500, 2016YFC0900501, 2016YFC0900504, 2016YFC1303904) from the National Key R&D Program of China, National Natural Science Foundation of China (81390540, 81390541, 81390544), and Chinese Ministry of Science and Technology (2011BAI09B01). The funders had no role in the study design, data collection, data analysis and interpretation, writing of the report, or the decision to submit the article for publication.