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

Published version
Peer-reviewed

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Authors

Haag, Andrea 
Henggeler, Adrian 

Abstract

The intracellular trafficking of growth factor receptors determines the activity of their downstream signaling pathways. Here, we show that the 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.

Description

Funder: Kanton of Zürich

Keywords

A431, C. elegans, CHORD, EGFR, HSP90, cell biology, chaperone, developmental biology, human, Animals, Caenorhabditis elegans, ErbB Receptors, HSP90 Heat-Shock Proteins, Humans, Phosphate-Binding Proteins, Protein Transport, Signal Transduction

Journal Title

Elife

Conference Name

Journal ISSN

2050-084X
2050-084X

Volume Title

9

Publisher

eLife Sciences Publications, Ltd
Sponsorship
Swiss National Science Foundation (31003A-166580)