Murine Leukemia Virus GlycoGag Antagonizes SERINC5 via the ER-phagy Receptor RETREG1
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Sunan Li
PROVIDER: PXD057978 | iProX | Sun Nov 17 00:00:00 GMT 2024
REPOSITORIES: iProX
Publications
ADAM17 is an HIV-1 Restriction Factor Antagonized by Nef.
Zheng Yong-Hui YH Li Qiuchen Q Li Sunan S Ye Bowei B Liang Jie J
Research square 20250625
Nef is an HIV-1 accessory protein critical to viral pathogenesis. While its role in immune evasion is well established, the mechanism by which Nef enhances virion infectivity remains incompletely understood. Here, we identify ADAM17 (TACE) as a host restriction factor through affinity purification-mass spectrometry. ADAM17 associates with HIV-1 Env in the endoplasmic reticulum (ER), reducing Env expression and incorporation into virions, leading to an approximately 100-fold reduction in infectiv ...[more]
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Project description: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.
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