Sekiya, Michiko, Maruko-Otake, Akiko, Hearn, Stephen, Sakakibara, Yasufumi, Fujisaki, Naoki, Suzuki, Emiko, Ando, Kanae, Iijima, Koichi M. (June 2017) EDEM Function in ERAD Protects against Chronic ER Proteinopathy and Age-Related Physiological Decline in Drosophila. Developmental Cell, 41 (6). 652-664.e5. ISSN 1534-5807
Abstract
Summary The unfolded protein response (UPR), which protects cells against accumulation of misfolded proteins in the ER, is induced in several age-associated degenerative diseases. However, sustained UPR activation has negative effects on cellular functions and may worsen disease symptoms. It remains unknown whether and how UPR components can be utilized to counteract chronic ER proteinopathies. We found that promotion of ER-associated degradation (ERAD) through upregulation of ERAD-enhancing α-mannosidase-like proteins (EDEMs) protected against chronic ER proteinopathy without inducing toxicity in a Drosophila model. ERAD activity in the brain decreased with aging, and upregulation of EDEMs suppressed age-dependent behavioral decline and extended the lifespan without affecting the UPR gene expression network. Intriguingly, EDEM mannosidase activity was dispensable for these protective effects. Therefore, upregulation of EDEM function in the ERAD protects against ER proteinopathy in vivo and thus represents a potential therapeutic target for chronic diseases.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | ER stress unfolded protein response UPR ER-associated degradation ERAD ERAD-enhancing α-mannosidase-like proteins EDEMs protein misfolding neurodegeneration aging Drosophila |
| Subjects: | organism description > animal > insect > Drosophila bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification |
| CSHL Authors: | |
| Communities: | CSHL labs > Spector lab |
| Depositing User: | Matt Covey |
| Date: | 19 June 2017 |
| Date Deposited: | 21 Jun 2017 19:46 |
| Last Modified: | 07 Jul 2021 14:00 |
| PMCID: | PMC5559287 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/35011 |
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