生物
蛋白质稳态
自噬
未折叠蛋白反应
细胞生物学
内质网
ATG8型
袋3
遗传学
细胞凋亡
作者
Matthew D. Smith,Margaret E Harley,Alain J. Kemp,Jimi Wills,Martin Lee,Mark J. Arends,Alex von Kriegsheim,Christian Behrends,Simon Wilkinson
标识
DOI:10.1016/j.devcel.2017.11.024
摘要
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.
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