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
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DOI：
10.1016/j.molcel.2019.03.034
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发表时间：
2019-06-06
期刊：
影响因子：
16
通讯作者：
Harper, J. Wade
中科院分区：
文献类型：
--
作者：
An, Heeseon;Ordureau, Alban;Harper, J. Wade
细胞对营养胁迫的反应是通过大自噬将胞质内容物运输到溶酶体进行降解。内质网（ER）作为自噬体的起始位点，也通过ER-吞噬（一种选择性自噬形式）对营养应激进行重塑。营养胁迫期间的定量蛋白质组分析确定了一个未经研究的单通道跨膜ER蛋白，TEX 264，作为ER-吞噬受体。TEX 264使用LC 3相互作用区（LIR）运输到ATG 8阳性斑点，这些斑点通常起始于三向ER小管连接处，随后与溶酶体融合。相互作用和邻近生物锡基化蛋白质组学以LIR依赖的方式鉴定了位于TEX 264附近的一组自噬调节蛋白和货物衔接子。全局蛋白质组学和ER-吞噬通量分析揭示了营养应激期间TEX 264（-/-）细胞中ER蛋白质组的稳定性。这项工作揭示了TEX 264作为一种未被识别的ER-吞噬受体，其在营养胁迫期间独立于其他候选ER-吞噬受体来重塑ER。
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.