2. Academic Validation
  3. TEX264 Is an Endoplasmic Reticulum-Resident ATG8-Interacting Protein Critical for ER Remodeling during Nutrient Stress

TEX264 Is an Endoplasmic Reticulum-Resident ATG8-Interacting Protein Critical for ER Remodeling during Nutrient Stress

  • Mol Cell. 2019 Jun 6;74(5):891-908.e10. doi: 10.1016/j.molcel.2019.03.034.
Heeseon An 1,  Alban Ordureau 1,  Joao A Paulo 1,  Christopher J Shoemaker 2,  Vladimir Denic 2,  J Wade Harper 3
Affiliations

Affiliations

  • 1 Department of Cell Biology, Blavatnik Institute of Harvard Medical School, Boston, MA 02115, USA.
  • 2 Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
  • 3 Department of Cell Biology, Blavatnik Institute of Harvard Medical School, Boston, MA 02115, USA. Electronic address: [email protected].
PMID: 31006537 DOI: 10.1016/j.molcel.2019.03.034
Abstract

Cells respond to nutrient stress by trafficking cytosolic contents to lysosomes for degradation via macroautophagy. The endoplasmic reticulum (ER) serves as an initiation site for autophagosomes and is also remodeled in response to nutrient stress through ER-phagy, a form of selective Autophagy. Quantitative proteome analysis during nutrient stress identified an unstudied single-pass transmembrane ER protein, TEX264, as an ER-phagy receptor. TEX264 uses an LC3-interacting region (LIR) to traffic into ATG8-positive puncta that often initiate from three-way ER tubule junctions and subsequently fuse with lysosomes. Interaction and proximity biotinylation proteomics identified a cohort of Autophagy regulatory proteins and cargo adaptors located near TEX264 in an LIR-dependent manner. Global proteomics and ER-phagy flux analysis revealed the stabilization of a cohort of ER proteins in TEX264-/- cells during nutrient stress. This work reveals TEX264 as an unrecognized ER-phagy receptor that acts independently of other candidate ER-phagy receptors to remodel the ER during nutrient stress.

Keywords

ER-phagy; TEX264; selective autophagy.

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