Translocon Component Sec62 Acts in Endoplasmic Reticulum Turnover During Stress Recovery

Overview

Journal Nat Cell Biol

Specialty Cell Biology

Date 2016 Oct 28

PMID 27749824

Citations 231

Authors

Fiorenza Fumagalli

Julia Noack

Timothy J Bergmann

Eduardo Cebollero

Giorgia Brambilla Pisoni

Elisa Fasana

Ilaria Fregno

Carmela Galli

Marisa Loi

Tatiana Solda

Rocco DAntuono

Andrea Raimondi

Martin Jung

Armin Melnyk

Stefan Schorr

Anne Schreiber

Luca Simonelli

Luca Varani

Caroline Wilson-Zbinden

Oliver Zerbe

Kay Hofmann

Matthias Peter

Manfredo Quadroni

Richard Zimmermann

Maurizio Molinari

Affiliations

Soon will be listed here.

Abstract

The endoplasmic reticulum (ER) is a site of protein biogenesis in eukaryotic cells. Perturbing ER homeostasis activates stress programs collectively called the unfolded protein response (UPR). The UPR enhances production of ER-resident chaperones and enzymes to reduce the burden of misfolded proteins. On resolution of ER stress, ill-defined, selective autophagic programs remove excess ER components. Here we identify Sec62, a constituent of the translocon complex regulating protein import in the mammalian ER, as an ER-resident autophagy receptor. Sec62 intervenes during recovery from ER stress to selectively deliver ER components to the autolysosomal system for clearance in a series of events that we name recovER-phagy. Sec62 contains a conserved LC3-interacting region in the C-terminal cytosolic domain that is required for its function in recovER-phagy, but is dispensable for its function in the protein translocation machinery. Our results identify Sec62 as a critical molecular component in maintenance and recovery of ER homeostasis.

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