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cTAGE5/MEA6 Regulates LBR Localization to Maintain Nuclear Envelope Integrity and Safeguard Against Aging
Yaqing Wang1, Pengyu Sun1,2, Fuqiang Yang1,2
1State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
Aging Cell
|July 31, 2025
Summary
The protein cTAGE5 (cytosolic tail-anchored protein containing an acidic domain 5) is crucial for nuclear envelope integrity. Its deficiency causes premature aging and cellular senescence by disrupting lamin B receptor localization.
Area of Science:
- Cell Biology
- Molecular Biology
- Aging Research
Background:
- The protein cTAGE5/MEA6 is known to be essential for COPII complex assembly, ER-to-Golgi trafficking, and secretion.
- The broader cellular functions of cTAGE5/MEA6 beyond protein transport remain largely unexplored.
Purpose of the Study:
- To investigate the potential roles of cTAGE5/MEA6 in cellular functions beyond its established role in protein trafficking.
- To elucidate the mechanisms underlying the observed phenotypes associated with cTAGE5/MEA6 deficiency.
Main Methods:
- Conditional knockout of cTAGE5 in mice and mouse embryonic fibroblast (MEF) cells.
- Analysis of nuclear structure, cell proliferation, and protein localization.
- Investigation of the interaction between cTAGE5 and lamin B receptor (LBR).
- Assessment of the P53/P21 senescence pathway activation.
Main Results:
- Conditional cTAGE5 knockout led to embryonic lethality and premature aging in adult mice.
- cTAGE5 deficiency in MEF cells resulted in abnormal nuclear structure and impaired cell proliferation.
- cTAGE5 was found to interact with LBR, and its loss disrupted LBR localization to the inner nuclear membrane, causing LBR retention in the ER.
- Disruption of LBR localization led to abnormal nuclear envelope morphology and cellular senescence, associated with P53/P21 pathway activation.
Conclusions:
- cTAGE5 plays a critical role in maintaining nuclear envelope integrity.
- cTAGE5 functions to prevent cellular senescence and animal aging by ensuring proper LBR localization and nuclear envelope structure.
- The findings reveal a novel function for cTAGE5 in nuclear biology and aging.
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