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 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 Facial Moisturiser 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 Tray (Set of 3) 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 in recycling endosomes to retrieve endocytosed EGFR, thereby sustaining its cell surface expression and, consequently, cancer cell growth.