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Purification of the Membrane Compartment for Endoplasmic Reticulum-associated Degradation of Exogenous Antigens in Cross-presentation
Published on: August 21, 2017
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Misfolded polypeptides are selectively recognized and transported toward aggresomes by a CED complex
Joori Park1,2, Yeonkyoung Park1,2, Incheol Ryu1,2
1Creative Research Initiatives Center for Molecular Biology of Translation, Korea University, Seoul 02841, Republic of Korea.
Nature Communications
|June 8, 2017
Summary
A newly discovered protein complex (CTIF-eEF1A1-DCTN1) targets misfolded proteins to aggresomes, enhancing cellular resistance to proteotoxic stress and preventing further misfolded protein synthesis.
Area of Science:
- Cellular Biology
- Molecular Biology
- Neuroscience
Background:
- Misfolded polypeptides are cleared by the ubiquitin-proteasome system (UPS).
- Impaired UPS leads to aggregate formation, aggresome sequestration, and aggrephagy.
- Aggresome formation is crucial for neurodegenerative proteinopathies but its mechanisms are unclear.
Purpose of the Study:
- To elucidate the molecular mechanisms of aggresome formation.
- To identify key players in the cellular response to misfolded polypeptides.
- To understand how cells cope with proteotoxic stress.
Main Methods:
- Investigated the role of the CTIF-eEF1A1-DCTN1 (CED) complex.
- Analyzed the targeting of misfolded polypeptides to aggresomes.
- Examined the impact of CED complex activity on gene expression and apoptosis.
Main Results:
- The CED complex links recognition and aggresomal targeting of misfolded polypeptides.
- CTIF sequestration into aggresomes halts synthesis of misfolded proteins.
- This pathway enhances cellular resistance to proteotoxic stress and apoptosis.
Conclusions:
- The CED complex acts as a crucial surveillance pathway for misfolded polypeptides.
- A novel gene expression regulatory network for coping with proteotoxic stress has been identified.
- This discovery sheds light on mechanisms relevant to neurodegenerative diseases.
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