The CHORD protein CHP-1 regulates EGF receptor trafficking and signaling in <i>C. elegans</i> and in human cells.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32053105.
- Also identified by DOI 10.7554/eLife.50986 and PMC identifier 7062474.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 <i>C. elegans</i>. Loss of <i>chp-1</i> 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 <i>chp-1(lf)</i> mutants, and the inhibition of <i>hsp-90</i> 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 <i>C. elegans</i>, 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.
Medical subject headings
- Caenorhabditis elegans
- Phosphate-Binding Proteins
- Signal Transduction