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Intrinsically Disordered Protein TEX264 Mediates ER-phagy

Author:
Chino, Haruka, Hatta, Tomohisa, Natsume, Tohru, Mizushima, Noboru
Source:
Molecular cell 2019 v.74 no.5 pp. 909-921.e6
ISSN:
1097-2765
Subject:
amino acid sequences, autophagy, endoplasmic reticulum, mutants, receptors
Abstract:
Certain proteins and organelles can be selectively degraded by autophagy. Typical substrates and receptors of selective autophagy have LC3-interacting regions (LIRs) that bind to autophagosomal LC3 and GABARAP family proteins. Here, we performed a differential interactome screen using wild-type LC3B and a LIR recognition-deficient mutant and identified TEX264 as a receptor for autophagic degradation of the endoplasmic reticulum (ER-phagy). TEX264 is an ER protein with a single transmembrane domain and a LIR motif. TEX264 interacts with LC3 and GABARAP family proteins more efficiently and is expressed more ubiquitously than previously known ER-phagy receptors. ER-phagy is profoundly blocked by deletion of TEX264 alone and almost completely by additional deletion of FAM134B and CCPG1. A long intrinsically disordered region of TEX264 is required for its ER-phagy receptor function to bridge the gap between the ER and autophagosomal membranes independently of its amino acid sequence. These results suggest that TEX264 is a major ER-phagy receptor.
Agid:
6443234