SNX32 Regulates Sorting and Trafficking of Activated EGFR to the Lysosomal Degradation Pathway

ABSTRACT SNX32 is a member of the evolutionarily conserved Phox (PX) homology domain‐ and Bin/Amphiphysin/Rvs (BAR) domain‐ containing sorting nexin (SNX‐BAR) family of proteins, which play important roles in sorting and membrane trafficking of endosomal cargoes. Although SNX32 shares the highest amino acid sequence homology with SNX6, and has been believed to function redundantly with SNX5 and SNX6 in retrieval of the cation‐independent mannose‐6‐phosphate receptor (CI‐MPR) from endosomes to the trans ‐Golgi network (TGN), its role(s) in intracellular protein trafficking remains largely unexplored. Here, we report that it functions in parallel with SNX1 in mediating epidermal growth factor (EGF)‐stimulated postendocytic trafficking of the epidermal growth factor receptor (EGFR). Moreover, SNX32 interacts directly with EGFR, and recruits SNX5 to promote sorting of EGF–EGFR into multivesicular bodies (MVBs) for lysosomal degradation. Thus, SNX32 functions distinctively from other SNX‐BAR proteins to mediate signaling‐coupled endolysosomal trafficking of EGFR.