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

被引：208

作者：

An, Heeseon ^{[1
]}

Ordureau, Alban ^{[1
]}

Paulo, Joao A. ^{[1
]}

Shoemaker, Christopher J. ^{[2
,3
]}

Denic, Vladimir ^{[2
]}

Harper, J. Wade ^{[1
]}

机构：

[1] Harvard Med Sch, Blavatnik Inst, Dept Cell Biol, Boston, MA 02115 USA

[2] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA

[3] Dartmouth Coll, Geisel Sch Med, Dept Biochem & Cell Biol, Hanover, NH 03755 USA

来源：

MOLECULAR CELL | 2019年 / 74卷 / 05期

关键词：

SELECTIVE AUTOPHAGY; MECHANISMS; TURNOVER;

D O I：

10.1016/j.molcel.2019.03.034

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 bio-tinylation 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.

引用

页码：891 / +

页数：28