How EGFR Gets Wrapped Up: Different Paths for Different Ligands

The epidermal growth factor receptor, or EGFR, helps cells grow and become specialized. But when things go wrong, EGFR can cause cancer. There are eight molecules, called ligands, that activate EGFR, with two main ones being epidermal growth factor (EGF) and transforming growth factor-α (TGF-α). Scientists once thought that a process called clathrin-mediated endocytosis was how EGFR gets taken inside cells after activation. But new findings show that there might be other paths too. When EGF and TGF-α trigger the receptor, clathrin plays a big role in moving EGFR inside the cell. However, for ligands like heparin-binding EGF-like growth factor (HB-EGF) and betacellulin (BTC), clathrin isn't the only one doing the job. There seems to be another unknown path that helps out. Interestingly, even if clathrin is partially knocked out, these other ligands can still use a tiny bit of clathrin to get EGFR inside the cell.Moreover, a protein called dynamin is crucial for EGFR to get taken into cells, no matter which ligand is used. When scientists disabled some paths that don't rely on clathrin but do need dynamin, it didn't affect how EGFR gets internalized. This indicates that EGFR uses the clathrin-mediated pathway most of the time, especially with EGF and TGF-α. But for ligands like HB-EGF and BTC, there might be an extra, unidentified path volunteering to help. These findings make us question if there are more hidden routes for EGFR to enter cells. Understanding these paths could open new doors for treating cancers linked to EGFR.