An unfolded putative transmembrane polypeptide, which can lead to endoplasmic reticulum stress, is a substrate of parkin
Open accessAbstract
A putative G protein-coupled transmembrane polypeptide, named Pael receptor, was identified as an interacting protein with Parkin, a gene product responsible for autosomal recessive juvenile Parkinsonism (AR-JP). When overexpressed in cells, this receptor tends to become unfolded, insoluble, and ubiquitinated in vivo. The insoluble Pael receptor leads to unfolded protein-induced cell death. Parkin specifically ubiquitinates this receptor in the presence of ubiquitin-conjugating enzymes resident in the endoplasmic reticulum and promotes the degradation of insoluble Pael receptor, resulting in suppression of the cell death induced by Pael receptor overexpression. Moreover, the insoluble form of Pael receptor accumulates in the brains of AR-JP patients. Here, we show that the unfolded Pael receptor is a substrate of Parkin, the accumulation of which may cause selective neuronal death in AR-JP.
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PARK2, the gene mutated in rare forms of Parkinson disease, is thought to work via a similar pathogenic mechanism.
“the gene mutated in rare forms of Parkinson disease, PARK2, is thought to work via a similar pathogenic mechanism.”
From Limb-Girdle Muscular Dystrophy Type 2H Associated with Mutation in TRIM32, a Putative E3-Ubiquitin–Ligase Gene (2002) · cites this paper as Imai et al. 2001
Neuronal death in Parkinson disease is thought to be a direct result of the accumulation of proteins that are no longer ubiquitinated by mutant forms of parkin and therefore are not degraded by the proteasome.
“The neuronal death seen in Parkinson disease is thought to be a direct result of the accumulation of proteins that are no longer ubiquitinated by mutant forms of parkin and that, therefore, are not degraded by the proteasome”
From Limb-Girdle Muscular Dystrophy Type 2H Associated with Mutation in TRIM32, a Putative E3-Ubiquitin–Ligase Gene (2002) · cites this paper as Imai et al. 2001
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- Authors
- Imai, Y., Soda, M., Inoue, H., Hattori, N., Mizuno, Y., & Takahashi, R.
- Affiliations
- RIKEN Center for Brain Science (JP)
- RIKEN (JP)
- Juntendo University (JP)
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2001-06
- Volume
- 105
- Issue
- 7
- Pages
- 891-902
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2142780460
- Cited by
- 1,050
- References
- 40
- Citations by year
- 2026: 7 · 2025: 14 · 2024: 18 · 2023: 18 · 2022: 22 · 2021: 21 · 2020: 24 · 2019: 19 · 2018: 18 · 2017: 31 · 2016: 23 · 2015: 31 · 2014: 29 · 2013: 39 · 2012: 33
- FWCI
- 62.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Ministry of Health and Welfare
- RIKEN Brain Science Institute
- Japan Society for the Promotion of Science
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- Parkin, endoplasmic reticulum stress, protein unfolding, ubiquitination, E2 ubiquitin-conjugating enzyme, G protein-coupled receptors, autosomal recessive juvenile parkinsonism, neuronal cell death, protein degradation, brain accumulation
- MeSH terms
- Acetylcysteine, Brain, Cells, Cultured, Endoplasmic Reticulum, Humans, Ligases, Microscopy, Fluorescence, Precipitin Tests, Protein Binding, Receptors, Cell Surface, Recombinant Fusion Proteins, Ubiquitins, Cysteine Proteinase Inhibitors, Cell Death, Protein Folding, Parkinsonian Disorders, Two-Hybrid System Techniques, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligases
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