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Intrinsically Disordered Protein TEX264 Mediates ER-phagy

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Chino, Haruka, Hatta, Tomohisa, Natsume, Tohru, Mizushima, Noboru·2019·Molecular Cell

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.

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Metadata

Authors
Chino, H., Hatta, T., Natsume, T., & Mizushima, N.
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2019-06
Volume
74
Issue
5
Pages
909-921.e6
ISSN
1097-2765 (ISSN-L)
OpenAlex
W2940394744
Cited by
364
References
17
FWCI
28.48
Type
journal article
Language
en
Open access
bronze
Funders
  • Japan Society for the Promotion of Science (25111005, 17J05822)
  • Japan Science and Technology Agency
  • Exploratory Research for Advanced Technology (JPMJER1702)

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Chino, H., Hatta, T., Natsume, T., & Mizushima, N. (2019). Intrinsically Disordered Protein TEX264 Mediates ER-phagy. Molecular Cell. https://doi.org/10.1016/j.molcel.2019.03.033

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