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The CHORD protein CHP-1 regulates EGF receptor trafficking and signaling in C. elegans and human cells

  1. Andrea Haag
  2. Michael Walser
  3. Adrian Henggeler
  4. Alex Hajnal  Is a corresponding author
  1. University of Zürich, Switzerland
Research Article
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Cite this article as: eLife 2020;9:e50986 doi: 10.7554/eLife.50986

Abstract

The intracellular trafficking of growth factor receptors determines the activity of their downstream signaling pathways. Here, we show that he putative HSP-90 co-chaperone CHP-1 acts as a regulator of EGFR trafficking in C. elegans. Loss of chp-1 causes the retention of the EGFR in the ER and decreases MAPK signaling. CHP-1 is specifically required for EGFR trafficking, as the localization of other transmembrane receptors is unaltered in chp-1(lf) mutants, and the inhibition of hsp-90 or other co-chaperones does not affect EGFR localization. The role of the CHP-1 homolog CHORDC1 during EGFR trafficking is conserved in human cells. Analogous to C. elegans, the response of CHORDC1-deficient A431 cells to EGF stimulation is attenuated, the EGFR accumulates in the ER and ERK2 activity decreases. Although CHP-1 has been proposed to act as a co-chaperone for HSP90, our data indicate that CHP-1 plays an HSP90-independent function in controlling EGFR trafficking through the ER.

Article and author information

Author details

  1. Andrea Haag

    Molecular Life Science, University of Zürich, Zürich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  2. Michael Walser

    Molecular Life Science, University of Zürich, Zürich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3506-4621
  3. Adrian Henggeler

    Molecular Life Science, University of Zürich, Zürich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  4. Alex Hajnal

    Molecular Life Science, University of Zürich, Zürich, Switzerland
    For correspondence
    alex.hajnal@imls.uzh.ch
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4098-3721

Funding

Swiss National Science Foundation (31003A-166580)

  • Alex Hajnal

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

Reviewing Editor

  1. Matthew Freeman, University of Oxford, United Kingdom

Publication history

  1. Received: August 9, 2019
  2. Accepted: February 12, 2020
  3. Accepted Manuscript published: February 13, 2020 (version 1)

Copyright

© 2020, Haag 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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