Clathrin adapters AP-1 and GGA2 support expression of epidermal growth factor receptor for cell growth

Clathrin adapters AP-1 and GGA2 support expression of epidermal growth factor receptor for cell growth

Blog Article

Abstract The role of Golgi/endosome-localized clathrin CS-1708 adapters in the maintenance of steady-state cell surface epidermal growth factor receptor (EGFR) is not well known.Here, we show that EGFR associates preferentially with both AP-1 and GGA2 in vitro.AP-1 depletion caused a reduction in the EGFR protein by promoting its lysosomal degradation.

Triple immunofluorescence microscopy and proximity ligation assays demonstrated that the interaction of EGFR with AP-1 or GGA2 occurred more frequently in Rab11-positive recycling endosomes than in Rab5-positive early endosomes.Biochemical recycling assay revealed that the depletion of AP-1 or GGA2 significantly suppressed EGFR recycling to the plasma membrane regardless of the EGF stimulation.Depletion of AP-1 or GGA2 also reduced cell contents of other tyrosine kinases, MET and ErbB4, and therefore, suppressed the growth of H1975 cancer cells in culture and xenograft model.

Moreover, AP-1 was expressed in endosomes at higher levels in some cancer tissues.Collectively, these results suggest that AP-1 and GGA2 function Media in recycling endosomes to retrieve endocytosed EGFR, thereby sustaining its cell surface expression and, consequently, cancer cell growth.