Translocon component Sec62 acts in endoplasmic reticulum turnover during stress recovery

• Published in: Nature cell biology Vol. 18; no. 11; pp. 1173 - 1184
• Main Authors: Fumagalli, Fiorenza, Noack, Julia, Bergmann, Timothy J., Cebollero, Eduardo, Pisoni, Giorgia Brambilla, Fasana, Elisa, Fregno, Ilaria, Galli, Carmela, Loi, Marisa, Soldà, Tatiana, D’Antuono, Rocco, Raimondi, Andrea, Jung, Martin, Melnyk, Armin, Schorr, Stefan, Schreiber, Anne, Simonelli, Luca, Varani, Luca, Wilson-Zbinden, Caroline, Zerbe, Oliver, Hofmann, Kay, Peter, Matthias, Quadroni, Manfredo, Zimmermann, Richard, Molinari, Maurizio
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-11-2016; Nature Publishing Group
• Subjects: 631/80/313/1463; 631/80/39; 631/80/642/1463; Animals; Autophagy; Autophagy (Cytology); Biochemistry; Biology; Biosynthesis; Cancer Research; Cell Biology; Composition; Developmental Biology; Endoplasmic reticulum; Endoplasmic Reticulum - metabolism; Endoplasmic Reticulum Stress - physiology; Enzymes; Health aspects; Homeostasis; Humans; Life Sciences; Membrane proteins; Membrane Transport Proteins - metabolism; Mice; Molecular Chaperones - metabolism; Physiological aspects; Protein Biosynthesis - physiology; Protein synthesis; Protein Transport - physiology; Proteins; Stem Cells; Translocation; Unfolded Protein Response - physiology; Switzerland; Germany
• ISSN: 1465-7392; 1476-4679
• DOI: 10.1038/ncb3423

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.
Fumagalli
et al.
 show that Sec62 delivers ER components to the autolysosome for clearance by acting as a receptor for autophagy protein LC3-II. This identifies Sec62 as a critical factor for selective ER turnover.