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

G Caldieri; E Barbieri; Gilda Nappo; A Raimondi; M Bonora; A Conte; LGGC Verhoef; S Confalonieri; MG Malabarba; F Bianchi; A Cuomo; T Bonaldi; E Martini; D Mazza; Paolo Pinton; C Tacchetti; Simona Polo; PP Di Fiore; S Sigismund

doi:10.1126/science.aah6152

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

G Caldieri, E Barbieri, Gilda Nappo, A Raimondi, M Bonora, A Conte, LGGC Verhoef, S Confalonieri, MG Malabarba, F Bianchi, A Cuomo, T Bonaldi, E Martini, D Mazza, Paolo Pinton, C Tacchetti, Simona Polo, PP Di Fiore, S Sigismund

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	617-624
Number of pages	8
Journal	Science
Volume	356
Issue number	6338
DOIs	https://doi.org/10.1126/science.aah6152
Publication status	Published - 2017

Access to Document

10.1126/science.aah6152

http://www.scopus.com/inward/record.url?scp=85019189969&partnerID=8YFLogxK

Fingerprint Dive into the research topics of 'Reticulon 3-dependent ER-PM contact sites control EGFR nonclathrin endocytosis'. Together they form a unique fingerprint.

Cite this

Caldieri, G., Barbieri, E., Nappo, G., Raimondi, A., Bonora, M., Conte, A., Verhoef, LGGC., Confalonieri, S., Malabarba, MG., Bianchi, F., Cuomo, A., Bonaldi, T., Martini, E., Mazza, D., Pinton, P., Tacchetti, C., Polo, S., Di Fiore, PP., & Sigismund, S. (2017). Reticulon 3-dependent ER-PM contact sites control EGFR nonclathrin endocytosis. Science, 356(6338), 617-624. https://doi.org/10.1126/science.aah6152

Reticulon 3-dependent ER-PM contact sites control EGFR nonclathrin endocytosis. / Caldieri, G; Barbieri, E; Nappo, Gilda; Raimondi, A; Bonora, M; Conte, A; Verhoef, LGGC; Confalonieri, S; Malabarba, MG; Bianchi, F ; Cuomo, A ; Bonaldi, T; Martini, E; Mazza, D; Pinton, Paolo; Tacchetti, C; Polo, Simona; Di Fiore, PP; Sigismund, S.

In: Science, Vol. 356, No. 6338, 2017, p. 617-624.

Research output: Contribution to journal › Article › peer-review

Caldieri, G, Barbieri, E, Nappo, G, Raimondi, A, Bonora, M, Conte, A, Verhoef, LGGC, Confalonieri, S, Malabarba, MG, Bianchi, F , Cuomo, A , Bonaldi, T, Martini, E, Mazza, D, Pinton, P, Tacchetti, C, Polo, S, Di Fiore, PP & Sigismund, S 2017, 'Reticulon 3-dependent ER-PM contact sites control EGFR nonclathrin endocytosis', Science, vol. 356, no. 6338, pp. 617-624. https://doi.org/10.1126/science.aah6152

Caldieri, G ; Barbieri, E ; Nappo, Gilda ; Raimondi, A ; Bonora, M ; Conte, A ; Verhoef, LGGC ; Confalonieri, S ; Malabarba, MG ; Bianchi, F ; Cuomo, A ; Bonaldi, T ; Martini, E ; Mazza, D ; Pinton, Paolo ; Tacchetti, C ; Polo, Simona ; Di Fiore, PP ; Sigismund, S. / Reticulon 3-dependent ER-PM contact sites control EGFR nonclathrin endocytosis. In: Science. 2017 ; Vol. 356, No. 6338. pp. 617-624.

@article{f687f358b86c43d68885b2e9d612dc23,

title = "Reticulon 3-dependent ER-PM contact sites control EGFR nonclathrin endocytosis",

abstract = "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. {\textcopyright} 2017, American Association for the Advancement of Science. All rights reserved.",

author = "G Caldieri and E Barbieri and Gilda Nappo and A Raimondi and M Bonora and A Conte and LGGC Verhoef and S Confalonieri and MG Malabarba and F Bianchi and A Cuomo and T Bonaldi and E Martini and D Mazza and Paolo Pinton and C Tacchetti and Simona Polo and {Di Fiore}, PP and S Sigismund",

year = "2017",

doi = "10.1126/science.aah6152",

language = "English",

volume = "356",

pages = "617--624",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6338",

}

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 -