TY  - JOUR
A1  - Forrester, Alison
A1  - De Leonibus, Chiara
A1  - Grumati, Paolo
A1  - Fasana, Elisa
A1  - Piemontese, Marilina
A1  - Staiano, Leopoldo
A1  - Fregno, Ilaria
A1  - Raimondi, Andrea
A1  - Marazza, Alessandro
A1  - Bruno, Gemma
A1  - Iavazzo, Maria
A1  - Intartaglia, Daniela
A1  - Seczynska, Marta
A1  - Anken, Eelco van
A1  - Conte, Ivan
A1  - De Matteis, Maria Antonietta
A1  - Đikić, Ivan
A1  - Molinari, Maurizio
A1  - Settembre, Carmine
T1  - A selective ER‐phagy exerts procollagen quality control via a Calnexin‐FAM134B complex
T2  - The EMBO journal
N2  - Autophagy is a cytosolic quality control process that recognizes substrates through receptor‐mediated mechanisms. Procollagens, the most abundant gene products in Metazoa, are synthesized in the endoplasmic reticulum (ER), and a fraction that fails to attain the native structure is cleared by autophagy. However, how autophagy selectively recognizes misfolded procollagens in the ER lumen is still unknown. We performed siRNA interference, CRISPR‐Cas9 or knockout‐mediated gene deletion of candidate autophagy and ER proteins in collagen producing cells. We found that the ER‐resident lectin chaperone Calnexin (CANX) and the ER‐phagy receptor FAM134B are required for autophagy‐mediated quality control of endogenous procollagens. Mechanistically, CANX acts as co‐receptor that recognizes ER luminal misfolded procollagens and interacts with the ER‐phagy receptor FAM134B. In turn, FAM134B binds the autophagosome membrane‐associated protein LC3 and delivers a portion of ER containing both CANX and procollagen to the lysosome for degradation. Thus, a crosstalk between the ER quality control machinery and the autophagy pathway selectively disposes of proteasome‐resistant misfolded clients from the ER.
KW  - autophagy
KW  - Calnexin
KW  - collagen
KW  - endoplasmic reticulum
KW  - FAM134B
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/52550
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-525500
SN  - 1460-2075
SN  - 0261-4189
N1  - © 2018 The Authors. Published under the terms of the CC BY 4.0 license
VL  - 38
IS  - 2, e99847
SP  - 1
EP  - 16
PB  - EMBO Press ; Wiley
CY  - Heidelberg ; Hoboken, NJ [u. a.]
ER  -