The clathrin adaptor complex-1 and Rab12 regulate post-golgi trafficking of WT epidermal growth factor receptor (EGFR)

The epidermal growth factor receptor (EGFR) plays important roles in cancer progression and is one of the major drug targets for targeted cancer therapy. Although fundamentally important, how newly synthesized EGFR is delivered to the cell surface to perform its cellular functions remains to be further investigated. In this study, we found using the approaches of gene knockout, siRNA knockdown, streptavidin pull-down, and co-immunoprecipitation assays that the clathrin adaptor complex-1 (AP-1) and Rab12 interact with EGFR and regulate the export of EGFR out of the trans-Golgi network (TGN). In addition, the tyrosine residue at the 998 position on human EGFR is critical to bind to AP-1, and this residue is important for TGN export of EGFR. We demonstrate that AP-1 and Rab12 are important for epidermal growth factor-induced phosphorylation of EGFR, cell elongation, and proliferation, suggesting that AP-1-mediated and Rab12-mediated postGolgi trafficking is important for EGFR signaling. Moreover, TGN export of the constitutively activated mutant form of EGFR (EGFRL858R) is independent of AP-1 and Rab12. Our results reveal insights into the molecular mechanisms that mediate the TGN-to-cell surface delivery of EGFR and indicate that TGN export of WT EGFR and EGFRL858R depends on different cellular factors.

Automated summary

This study investigates the mechanisms of how newly synthesized EGFR is transported from the trans-Golgi network (TGN) to the cell surface. The researchers identify that the clathrin adaptor complex-1 (AP-1) and Rab12 interact with EGFR and regulate its export from the TGN. They also find that a specific tyrosine residue on EGFR is critical for binding to AP-1 and for TGN export. Moreover, AP-1 and Rab12 are shown to be important for EGFR signaling and cellular functions. The study provides insights into the molecular mechanisms underlying EGFR transport and highlights the role of AP-1 and Rab12 in EGFR trafficking.