TY - JOUR
T1 - Reticulon 3-dependent ER-PM contact sites control EGFR nonclathrin endocytosis
AU - Caldieri, G
AU - Barbieri, E
AU - Nappo, Gilda
AU - Raimondi, A
AU - Bonora, M
AU - Conte, A
AU - Verhoef, LGGC
AU - Confalonieri, S
AU - Malabarba, MG
AU - Bianchi, F
AU - Cuomo, A
AU - Bonaldi, T
AU - Martini, E
AU - Mazza, D
AU - Pinton, Paolo
AU - Tacchetti, C
AU - Polo, Simona
AU - Di Fiore, PP
AU - Sigismund, S
PY - 2017
Y1 - 2017
N2 - 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 critical for EGFR/CD147-NCE, promoting the creation of plasma membrane (PM)-ER contact sites that were required for the formation and/or maturation of NCE invaginations. Ca 2+ release at these sites, triggered by inositol 1,4,5-trisphosphate (IP 3 )-dependent activation of ER Ca 2+ channels, was needed for the completion of EGFR internalization. Thus, we identified a mechanism of EGFR endocytosis that relies on ER-PM contact sites and local Ca 2+ signaling. © 2017, American Association for the Advancement of Science. All rights reserved.
AB - 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 critical for EGFR/CD147-NCE, promoting the creation of plasma membrane (PM)-ER contact sites that were required for the formation and/or maturation of NCE invaginations. Ca 2+ release at these sites, triggered by inositol 1,4,5-trisphosphate (IP 3 )-dependent activation of ER Ca 2+ channels, was needed for the completion of EGFR internalization. Thus, we identified a mechanism of EGFR endocytosis that relies on ER-PM contact sites and local Ca 2+ signaling. © 2017, American Association for the Advancement of Science. All rights reserved.
U2 - 10.1126/science.aah6152
DO - 10.1126/science.aah6152
M3 - Article
VL - 356
SP - 617
EP - 624
JO - Science
JF - Science
SN - 0036-8075
IS - 6338
ER -