EDEM1 Regulates Amyloid Precursor Protein (APP) Metabolism and Amyloid-β Production
| Autor: | Jowita Nowakowska-Gołacka, Justyna Czapiewska, Hanna Sominka, Natalia Sowa-Rogozińska, Monika Słomińska-Wojewódzka |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Protein Folding
Glycosylation QH301-705.5 Golgi Apparatus Endoplasmic Reticulum Catalysis Article Cell Line Inorganic Chemistry Amyloid beta-Protein Precursor Cytosol Alzheimer Disease alpha-Mannosidase Cell Line Tumor mental disorders endoplasmic reticulum degradation-enhancing α-mannosidase-like 1 protein (EDEM1) amyloid-β precursor protein (APP) endoplasmic reticulum-associated degradation (ERAD) amyloid-β (Aβ) endoplasmic reticulum (ER) protein degradation protein quality control Humans Biology (General) Physical and Theoretical Chemistry QD1-999 Molecular Biology Spectroscopy Amyloid beta-Peptides Organic Chemistry Brain Membrane Proteins General Medicine Endoplasmic Reticulum-Associated Degradation Computer Science Applications Chemistry HEK293 Cells |
| Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences; Volume 23; Issue 1; Pages: 117 International Journal of Molecular Sciences, Vol 23, Iss 117, p 117 (2022) |
| ISSN: | 1422-0067 |
| Popis: | Endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like protein 1 (EDEM1) is a quality control factor directly involved in the endoplasmic reticulum-associated degradation (ERAD) process. It recognizes terminally misfolded proteins and directs them to retrotranslocation which is followed by proteasomal degradation in the cytosol. The amyloid-β precursor protein (APP) is synthesized and N-glycosylated in the ER and transported to the Golgi for maturation before being delivered to the cell surface. The amyloidogenic cleavage pathway of APP leads to production of amyloid-β (Aβ), deposited in the brains of Alzheimer’s disease (AD) patients. Here, using biochemical methods applied to human embryonic kidney, HEK293, and SH-SY5Y neuroblastoma cells, we show that EDEM1 is an important regulatory factor involved in APP metabolism. We find that APP cellular levels are significantly reduced after EDEM1 overproduction and are increased in cells with downregulated EDEM1. We also report on EDEM1-dependent transport of APP from the ER to the cytosol that leads to proteasomal degradation of APP. EDEM1 directly interacts with APP. Furthermore, overproduction of EDEM1 results in decreased Aβ40 and Aβ42 secretion. These findings indicate that EDEM1 is a novel regulator of APP metabolism through ERAD. |
| Databáze: | OpenAIRE |
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