TY - UNPB
T1 - A cross-kingdom conserved ER-phagy receptor maintains endoplasmic reticulum homeostasis during stress
AU - Stephani, Madlen
AU - Picchianti, Lorenzo
AU - Gajic, Alexander
AU - Beveridge, Rebecca
AU - Skarwan, Emilio
AU - Sanchez de Medina Hernandez, Victor
AU - Mohseni, Azadeh
AU - Clavel, Marion
AU - Zeng, Yonglung
AU - Naumann, Christin
AU - Matuszkiewicz, Mateusz
AU - Turco, Eleonora
AU - Loefke, Christian
AU - Li, Baiying
AU - Durnberger, Gerhard
AU - Schutzbier, Michael
AU - Chen, Hsiao Tieh
AU - Abdrakhmanov, Alibek
AU - Savova, Adriana
AU - Chia, Khong-Sam
AU - Djamei, Armin
AU - Schaffner, Irene
AU - Abel, Steffen
AU - Jiang, Liwen
AU - Mechtler, Karl
AU - Ikeda, Fumiyo
AU - Martens, Sascha
AU - Clausen, Tim
AU - Dagdas, Yasin
PY - 2020/3/24
Y1 - 2020/3/24
N2 - Eukaryotes have evolved various quality control mechanisms to promote proteostasis in the ER. Selective removal of certain ER domains via autophagy (termed as ER-phagy) has emerged as a major quality control mechanism. However, the degree to which ER-phagy is employed by other branches of ER-quality control remains largely elusive. Here, we identify a cytosolic protein, C53, that is specifically recruited to autophagosomes during ER-stress, in both plant and mammalian cells. C53 interacts with ATG8 via a distinct binding epitope, featuring a shuffled ATG8 interacting motif (sAIM). C53 senses proteotoxic stress in the ER lumen by forming a tripartite receptor complex with the ER-associated ufmylation ligase UFL1 and its membrane adaptor DDRGK1. The C53/UFL1/DDRGK1 receptor complex is activated by stalled ribosomes and induces the degradation of internal or passenger proteins in the ER. Consistently, the C53 receptor complex and ufmylation mutants are highly susceptible to ER stress. Thus, C53 forms an ancient quality control pathway that bridges selective autophagy with ribosome-associated quality control at the ER.
AB - Eukaryotes have evolved various quality control mechanisms to promote proteostasis in the ER. Selective removal of certain ER domains via autophagy (termed as ER-phagy) has emerged as a major quality control mechanism. However, the degree to which ER-phagy is employed by other branches of ER-quality control remains largely elusive. Here, we identify a cytosolic protein, C53, that is specifically recruited to autophagosomes during ER-stress, in both plant and mammalian cells. C53 interacts with ATG8 via a distinct binding epitope, featuring a shuffled ATG8 interacting motif (sAIM). C53 senses proteotoxic stress in the ER lumen by forming a tripartite receptor complex with the ER-associated ufmylation ligase UFL1 and its membrane adaptor DDRGK1. The C53/UFL1/DDRGK1 receptor complex is activated by stalled ribosomes and induces the degradation of internal or passenger proteins in the ER. Consistently, the C53 receptor complex and ufmylation mutants are highly susceptible to ER stress. Thus, C53 forms an ancient quality control pathway that bridges selective autophagy with ribosome-associated quality control at the ER.
KW - endoplasmic reticulum
KW - heterogeneous cellular network
KW - autophagy
U2 - 10.1101/2020.03.18.995316
DO - 10.1101/2020.03.18.995316
M3 - Working paper
BT - A cross-kingdom conserved ER-phagy receptor maintains endoplasmic reticulum homeostasis during stress
CY - Cold Spring Harbor, NY.
ER -