Reticulon 3-dependent ER-PM contact sites control EGFR nonclathrin endocytosis

The integration of endocytic routes is critical to regulate receptor signaling. A nonclathrin endocytic (NCE) pathway of the epidermal growth factor receptor (EGFR) is activated at high ligand concentrations and targets receptors to degradation, attenuating signaling. Here we performed an unbiased molecular characterization of EGFR-NCE. We identified NCE-specific regulators, including the endoplasmic reticulum (ER)–resident protein reticulon 3 (RTN3) and a specific cargo, CD147. RTN3 was c