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

• DOI: 10.1126/science.aah6152
• Publication Date: 2017-05-11T18:10:40Z
• Authors: Giusi Caldieri; Elisa Barbieri; Gilda Nappo; Andrea Raimondi; Massimo Bonora; Alexia Conte; Lisette G. G. C. ...; Stefano Confalonieri; Maria Grazia Mala...; Fabrizio Bianchi; Alessandro Cuomo; Tiziana Bonaldi; Emanuele Martini; Davide Mazza; Paolo Pinton; Carlo Tacchetti; Simona Polo; Pier Paolo Di Fiore; Sara Sigismund
• Keywords: Basigin; Calcium Signaling; Carrier Proteins; Cell Line; Cell Membrane; Endoplasmic Reticulum; Humans; Membrane Proteins; Nerve Tissue Proteins; Receptor, Epidermal Growth Factor; Endocytosis; Multidisciplinary; ErbB Receptors; Basigin; Calcium Signaling; Carrier Proteins; Cell Line; Cell Membrane; Endoplasmic Reticulum; Humans; Membrane Proteins; Nerve Tissue Proteins; Receptor, Epidermal Growth Factor; Endocytosis; Cell Membrane; Basigin; Humans; Membrane Proteins; Nerve Tissue Proteins; Calcium Signaling; Carrier Proteins; Endoplasmic Reticulum; Endocytosis; Cell Line

ER-PM contacts in nonclathrin endocytosis

The epidermal growth factor receptor (EGFR) is internalized through both clathrin-mediated endocytosis and nonclathrin endocytosis (NCE). The two pathways act in concert to sustain EGFR signaling or its long-term attenuation. The mechanistic underpinnings of EGFR-NCE are unclear. Caldieri et al. used a variety of cell and molecular biology approaches to identify nine regulators of EGFR-NCE (see the Perspective by Tan and Anderson). They also identified an additional cargo of the pathway (CD147). One of the regulators of the pathway was the endoplasmic reticulum (ER)-resident protein reticulon 3 (RTN3). Unexpectedly, EGFR-NCE required the formation of specific contacts between the plasma membrane (PM) and the cortical ER, mediated by RTN3. ER-PM contact sites were required in the very early steps of the internalization process for the maturation of NCE tubular intermediates.

Science , this issue p. 617 ; see also p. 584