Institute of Molecular Life Sciences, University of Zürich, Winterthurerstrasse, Switzerland.
Molecular Life Science Zürich PhD Program, Zürich, Switzerland.
Elife. 2020 Feb 13;9:e50986. doi: 10.7554/eLife.50986.
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 . Loss of 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 mutants, and the inhibition of 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 , 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.
细胞内生长因子受体的运输决定了其下游信号通路的活性。在这里，我们发现假定的 HSP-90 共伴侣 CHP-1 作为 EGFR 在. 中的运输调节剂。缺失 导致 EGFR 在 ER 中的滞留，并降低 MAPK 信号。CHP-1 是 EGFR 运输所必需的，因为其他跨膜受体的定位在 突变体中没有改变，并且抑制 或其他共伴侣不会影响 EGFR 定位。CHP-1 同源物 CHORDC1 在 EGFR 运输过程中的作用在人类细胞中是保守的。类似于 ，缺乏 CHORDC1 的 A431 细胞对 EGF 刺激的反应减弱，EGFR 在 ER 中积累，ERK2 活性降低。尽管已经提出 CHP-1 作为 HSP90 的共伴侣发挥作用，但我们的数据表明，CHP-1 通过 ER 控制 EGFR 运输发挥 HSP90 独立的功能。
