Intrinsically Disordered Protein TEX264 Mediates ER-phagy

• Published in: Molecular cell Vol. 74; no. 5; pp. 909 - 921.e6
• Main Authors: Chino, Haruka, Hatta, Tomohisa, Natsume, Tohru, Mizushima, Noboru
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 06.06.2019
• Subjects: Amino Acid Sequence - genetics; Autophagy - genetics; Autophagy-Related Proteins - chemistry; Autophagy-Related Proteins - genetics; Cell Cycle Proteins - genetics; Endoplasmic Reticulum - chemistry; Endoplasmic Reticulum - genetics; Endoplasmic Reticulum Stress - genetics; ER-phagy; Humans; Intracellular Signaling Peptides and Proteins; Intrinsically Disordered Proteins - chemistry; Intrinsically Disordered Proteins - genetics; intrinsically disordered region; Membrane Proteins; Microtubule-Associated Proteins - genetics; Neoplasm Proteins - genetics; organellar contact site; Proteolysis; selective autophagy; organellar contact site; intrinsically disordered region; ER-phagy; selective autophagy
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2019.03.033

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. [Display omitted] •TEX264 was identified by a differential LC3B-interactome screen•TEX264 is an ER transmembrane protein with an LC3-interacting region•TEX264 acts as a major receptor for autophagic degradation of the ER (ER-phagy)•A disordered region in TEX264 bridges the gap between the ER and autophagosomes Macroautophagy can selectively recognize and degrade organelles such as the ER. Chino et al. identified TEX264 as a receptor for autophagic degradation of the ER (ER-phagy). A long intrinsically disordered region in TEX264 is required for its ER-phagy receptor function to bridge the gap between the ER and autophagosomes.