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bioRxiv · 10.1101/745984

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

Haag, A.·Walser, M.·Henggeler, A.·Hajnal, A.
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Abstract

The intracellular trafficking of growth factor receptors determines the activity of their downstream signaling pathways. The putative co-chaperone CHP-1 acts as a regulator of EGFR trafficking during C.elegans vulval development. Loss of chp-1 causes the retention of the EGFR in the ER and decreased MAPK signaling. CHP-1 functions specifically, as the localization of other receptors is unaltered in chp-1(lf) mutants, and inhibiting other co-chaperones does not affect EGFR localization. The role of CHP-1 during EGFR trafficking is conserved in humans. Analogous to C.elegans, the response of CHP-1-deficient human cells to EGF stimulation is attenuated, the EGFR accumulates in the ER and ERK2 activity is decreased. Although CHP-1 has been proposed to act as a co-chaperone for HSP90, our data indicate an HSP90-independent function of CHP-1. The identification of CHP-1 as a regulator of EGFR trafficking opens the possibility to identify small molecule chaperone inhibitors targeting the EGFR pathway with increased selectivity.

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Haag, A., Walser, M., Henggeler, A., Hajnal, A.. 2019-08-25. The CHORD protein CHP-1 regulates EGF receptor trafficking and signaling in C. elegans and human cells. https://doi.org/10.1101/745984

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