CCPG1 Is a Non-canonical Autophagy Cargo Receptor Essential for ER-Phagy and Pancreatic ER Proteostasis.
CCPG1 Is a Non-canonical Autophagy Cargo Receptor Essential for ER-Phagy and Pancreatic ER Proteostasis.
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DOI：
10.1016/j.devcel.2017.11.024
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发表时间：
2018-01-22
影响因子：
11.8
通讯作者：
Wilkinson S
中科院分区：
文献类型：
--
作者：
Smith MD;Harley ME;Kemp AJ;Wills J;Lee M;Arends M;von Kriegsheim A;Behrends C;Wilkinson S
ER的选择性自噬机制，称为ER-吞噬，需要分子描绘，特别是在体内。目前尚不清楚这些事件如何控制ER蛋白质稳态和细胞健康。在这里，我们确定细胞周期进展基因1（CCPG 1），ER驻留蛋白，没有已知的生理作用，作为一个非典型的货物受体，直接结合核心自噬蛋白通过LIR基序哺乳动物ATG 8蛋白，并独立地和通过离散基序，FIP 200。这些相互作用促进ER-吞噬。CCPG 1基因可由未折叠蛋白反应诱导，因此直接将ER应激与ER-吞噬联系起来。在体内，CCPG 1防止ER管腔蛋白聚集和随后的未折叠蛋白反应过度活化和外分泌胰腺的组织损伤。因此，通过鉴定这种自噬蛋白，我们描述了一个意想不到的ER-吞噬的分子机制，并提供证据表明，这可能是生理相关的ER管腔蛋白质稳态。CCPG 1是哺乳动物内质网应激诱导的内质网自噬货物受体，CCPG 1通过不同的肽基序直接与ATG 8蛋白和FIP 200结合，CCPG 1溶酶体降解和内质网自噬都需要这些相互作用，CCPG 1在体内维持胰腺腺泡细胞正常的内质网腔蛋白稳态。Smith等人显示ER膜驻留蛋白CCPG 1是ER应激反应的效应子，通过与ATG 8和FIP 200的相互作用驱动ER-吞噬。CCPG 1在体内维持胰腺腺泡细胞内的ER腔蛋白稳态。
Mechanisms of selective autophagy of the ER, known as ER-phagy, require molecular delineation, particularly in vivo. It is unclear how these events control ER proteostasis and cellular health. Here, we identify cell-cycle progression gene 1 (CCPG1), an ER-resident protein with no known physiological role, as a non-canonical cargo receptor that directly binds to core autophagy proteins via an LIR motif to mammalian ATG8 proteins and, independently and via a discrete motif, to FIP200. These interactions facilitate ER-phagy. The CCPG1 gene is inducible by the unfolded protein response and thus directly links ER stress to ER-phagy. In vivo, CCPG1 protects against ER luminal protein aggregation and consequent unfolded protein response hyperactivation and tissue injury of the exocrine pancreas. Thus, via identification of this autophagy protein, we describe an unexpected molecular mechanism of ER-phagy and provide evidence that this may be physiologically relevant in ER luminal proteostasis. CCPG1 is an ER stress-inducible ER-phagy cargo receptor in mammals CCPG1 binds directly to ATG8 proteins and FIP200 via distinct peptide motifs CCPG1 lysosomal degradation and ER-phagy both require these interactions CCPG1 maintains normal ER luminal proteostasis in pancreatic acinar cells in vivo The mechanisms and physiological functions of ER autophagy (ER-phagy) are incompletely understood. Smith et al. show that the ER membrane-resident protein CCPG1 is an effector of ER stress responses, driving ER-phagy via interaction with ATG8 and FIP200. CCPG1 maintains ER luminal proteostasis within pancreatic acinar cells in vivo.
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影响因子：
10.5
作者：
Chen S;Wang C;Yeo S;Liang CC;Okamoto T;Sun S;Wen J;Guan JL
通讯作者：
Guan JL
影响因子：
4.8
作者：
Grasso, Daniel;Ropolo, Alejandro;Vaccaro, Maria I.
通讯作者：
Vaccaro, Maria I.
影响因子：
16.8
作者：
Gammoh, Noor;Florey, Oliver;Overholtzer, Michael;Jiang, Xuejun
通讯作者：
Jiang, Xuejun
影响因子：
16
作者：
Heo JM;Ordureau A;Paulo JA;Rinehart J;Harper JW
通讯作者：
Harper JW
DOI：
10.1038/nrm.2016.74
发表时间：
2016-09
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Farré JC;Subramani S
通讯作者：
Subramani S