CALCOCO1 acts with VAMP-associated proteins to mediate ER-phagy.

The EMBO Journal
Thaddaeus Mutugi NthigaTerje Johansen

Abstract

The endoplasmic reticulum (ER) plays important roles in protein synthesis and folding, and calcium storage. The volume of the ER and expression of its resident proteins are increased in response to nutrient stress. ER-phagy, a selective form of autophagy, is involved in the degradation of the excess components of the ER to restore homeostasis. Six ER-resident proteins have been identified as ER-phagy receptors so far. In this study, we have identified CALCOCO1 as a novel ER-phagy receptor for the degradation of the tubular ER in response to proteotoxic and nutrient stress. CALCOCO1 is a homomeric protein that binds directly to ATG8 proteins via LIR- and UDS-interacting region (UIR) motifs acting co-dependently. CALCOCO1-mediated ER-phagy requires interaction with VAMP-associated proteins VAPA and VAPB on the ER membranes via a conserved FFAT-like motif. Depletion of CALCOCO1 causes expansion of the ER and inefficient basal autophagy flux. Unlike the other ER-phagy receptors, CALCOCO1 is peripherally associated with the ER. Therefore, we define CALCOCO1 as a soluble ER-phagy receptor.

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Citations

Nov 20, 2020·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Mohamed A EldeebDoaa S Salah El-Din
Jan 24, 2021·Molecular Metabolism·Imke L LemmerAlexander Bartelt
Dec 18, 2020·Plants·Yan Bao, Diane C Bassham
Jan 30, 2021·Trends in Biochemical Sciences·Susan Ferro-NovickJeffrey L Brodsky
Nov 24, 2020·Oxidative Medicine and Cellular Longevity·Natalia Jimenez-Moreno, Jon D Lane
Mar 11, 2021·Developmental Cell·Dannah R Miller, Andrew Thorburn
Mar 18, 2021·The FEBS Journal·Andrea Gubas, Ivan Dikic
Apr 20, 2021·The Journal of Cell Biology·Thaddaeus Mutugi NthigaTerje Johansen
May 18, 2021·The Journal of Cell Biology·Ai Yamamoto
Jun 15, 2021·Molecular Aspects of Medicine·Hui QianWen-Xing Ding
Jul 27, 2021·Frontiers in Cell and Developmental Biology·Ming YangLin Sun
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Nov 18, 2021·The FEBS Journal·Saori Noguchi, Shigeomi Shimizu
Jan 13, 2022·The Journal of Cell Biology·Suzan KorsMichael Schrader

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Datasets Mentioned

BETA
GM130
PXD018894

Methods Mentioned

BETA
lipidation
confocal microscopy
immunoprecipitation
pull down
transfection
transfections
antisense oligonucleotides
PCR
Protein Assay

Software Mentioned

Fiji
CHOPCHOP
Huygens Volume Imaging
CALCOCO1
MaxQuant
Volocity
ZEN
CellDiscoverer
CALCOCO
ImageJ

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