COP I and II Dependent Trafficking Controls ER-associated Degradation in Mammalian Cells

Overview

Journal iScience

Publisher Cell Press

Date 2023 Mar 6

PMID 36876137

Authors

Navit Ogen-Shtern

Chieh Chang

Haddas Saad

Niv Mazkereth

Chaitanya Patel

Marina Shenkman

Gerardo Z Lederkremer

Affiliations

Soon will be listed here.

Abstract

Misfolded proteins and components of the endoplasmic reticulum (ER) quality control and ER associated degradation (ERAD) machineries concentrate in mammalian cells in the pericentriolar ER-derived quality control compartment (ERQC), suggesting it as a staging ground for ERAD. By tracking the chaperone calreticulin and an ERAD substrate, we have now determined that the trafficking to the ERQC is reversible and recycling back to the ER is slower than the movement in the ER periphery. The dynamics suggest vesicular trafficking rather than diffusion. Indeed, using dominant negative mutants of ARF1 and Sar1 or the drugs Brefeldin A and H89, we observed that COPI inhibition causes accumulation in the ERQC and increases ERAD, whereas COPII inhibition has the opposite effect. Our results suggest that targeting of misfolded proteins to ERAD involves COPII-dependent transport to the ERQC and that they can be retrieved to the peripheral ER in a COPI-dependent manner.

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