TY - JOUR T1 - The CHORD protein CHP-1 regulates EGF receptor trafficking and signaling in <em>C. elegans</em> and in human cells JF - bioRxiv DO - 10.1101/745984 SP - 745984 AU - Andrea Haag AU - Michael Walser AU - Adrian Henggeler AU - Alex Hajnal Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/08/25/745984.abstract N2 - 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. ER -