Proteomics,Multiomics

Dataset Information

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FAM134B oligomerization drives ER membrane scission for ER-phagy


ABSTRACT: ER degradation by selective autophagy (ER-phagy) is crucial for ER homeostasis. However, it remains unclear how ER scission is regulated for subsequent autophagosomal sequestration and lysosomal degradation. Here, we show that oligomer formation of FAM134B (also referred to as reticulophagy regulator 1 or RETREG1) through its Reticulon domain was required for membrane fragmentation in vitro and ER-phagy in vivo. Under ER stress conditions, activated CAMK2B phosphorylated the Reticulon domain of FAM134B, which enhanced FAM134B oligomerization and activity in membrane fragmentation to accommodate high demand of ER-phagy. Unexpectedly, FAM134BG216R, a variant derived from a type II HSAN patient, exhibited gain-of-function defects, such as hyperactive self-association and membrane scission, which resulted in excessive ER-phagy and sensory neuron death. Therefore, this study revealed a mechanism of ER membrane fragmentation in ER-phagy, along with a signaling pathway in regulating ER turnover, and suggested a potential implication of excessive selective autophagy in human diseases.

INSTRUMENT(S): LTQ Orbitrap Velos, TripleTOF 5600

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Jingzi Zhang  

LAB HEAD: Qiming Sun

PROVIDER: PXD016661 | Pride | 2020-01-09

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
20171029_03.wiff Wiff
20171029_03.wiff.scan Wiff
20171029_04.wiff Wiff
20171029_04.wiff.scan Wiff
20171029_SQM_02_PeptideSummary.txt Txt
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Publications

FAM134B oligomerization drives endoplasmic reticulum membrane scission for ER-phagy.

Jiang Xiao X   Wang Xinyi X   Ding Xianming X   Du Mengjie M   Li Boran B   Weng Xialian X   Zhang Jingzi J   Li Lin L   Tian Rui R   Zhu Qi Q   Chen She S   Wang Liang L   Liu Wei W   Fang Lei L   Neculai Dante D   Sun Qiming Q  

The EMBO journal 20200113 5


Degradation of endoplasmic reticulum (ER) by selective autophagy (ER-phagy) is crucial for ER homeostasis. However, it remains unclear how ER scission is regulated for subsequent autophagosomal sequestration and lysosomal degradation. Here, we show that oligomerization of ER-phagy receptor FAM134B (also referred to as reticulophagy regulator 1 or RETREG1) through its reticulon-homology domain is required for membrane fragmentation in vitro and ER-phagy in vivo. Under ER-stress conditions, activa  ...[more]

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