The CHORD protein CHP-1 regulates EGF receptor trafficking and signaling in C. elegans and human cells
- University of Zürich, Switzerland
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.
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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.
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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The CHORD protein CHP-1 regulates EGF receptor trafficking and signaling in C. elegans and human cells
eLife 9:e50986.
https://doi.org/10.7554/eLife.50986
