ArticleMolecular biology of the cell2007
Parkin-mediated monoubiquitination of the PDZ protein PICK1 regulates the activity of acid-sensing ion channels.
Article in Molecular biology of the cell, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 1 of them a synthesis that pooled it.
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Who cites it
86 citing papers in PubMed, 1 synthesis or guideline pooled it, 135 citations in OpenAlex.
- The Role of ASIC1a in Inflammatory Immune Diseases: A Potential Therapeutic Target.Frontiers in pharmacology · 2022Pooled it
- Protein interacting with C-kinase 1 is correlated to prognosis and immune infiltrates of gastric cancer.Discover oncology · 2025Article
- The Proteomic Landscape of Parkin-Deficient and Parkin-Overexpressing Rat Nucleus Accumbens: An Insight into the Role of Parkin in Methamphetamine Use Disorder.Biomolecules · 2025Article
- Ubiquitination of Metabotropic Glutamate Receptors and Associated Synaptic ProteinsJournal of cellular signaling · 2025Article
- Sodium arsenite induces aggresome formation by promoting PICK1 BAR domain homodimer formation.Molecular biology of the cell · 2024Article
- PARKIN is not required to sustain OXPHOS function in adult mammalian tissues.NPJ Parkinson's disease · 2024Article
- Activation of CaCell death and differentiation · 2024Article
- Overexpression of Parkin in the Neuronal Progenitor Cells from a Patient with Parkinson's Disease Shifts the Transcriptome Towards the Normal State.Molecular neurobiology · 2023Article
- Triggering of Major Brain Disorders by Protons and ATP: The Role of ASICs and P2X Receptors.Neuroscience bulletin · 2023Review
- The Role of Zinc in Modulating Acid-Sensing Ion Channel Function.Biomolecules · 2023Review
- Article
- Parkin Inhibits Static Mechanical Pain by Suppressing Membrane Trafficking of Mechano-transducing Ion Channel TACAN.Neuroscience bulletin · 2022Article
- Acid-Sensing Ion Channel 2: Function and Modulation.Membranes · 2022Review
- A review for the pharmacological effects of paeoniflorin in the nervous system.Frontiers in pharmacology · 2022Review
- Regulation of acid-sensing ion channels by protein binding partners.Channels (Austin, Tex.) · 2021Article
- Protein S-nitrosylation and oxidation contribute to protein misfolding in neurodegeneration.Free radical biology & medicine · 2021Review
- Protein interacting with C-kinase 1 is involved in epithelial-mesenchymal transformation and suppresses progress of gastric cancer.Medical oncology (Northwood, London, England) · 2021Article
- Ubiquitin signalling in neurodegeneration: mechanisms and therapeutic opportunities.Cell death and differentiation · 2021Review
- Neurodegenerative Disease: What Potential Therapeutic Role of Acid-Sensing Ion Channels?Frontiers in cellular neuroscience · 2021Review
- Pharmacological antagonism of kainate receptor rescues dysfunction and loss of dopamine neurons in a mouse model of human parkin-induced toxicity.Cell death & disease · 2020Article
26 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in the parkin gene result in an autosomal recessive juvenile-onset form of Parkinson's disease. As an E3 ubiquitin-ligase, parkin promotes the attachment of ubiquitin onto specific substrate proteins. Defects in the ubiquitination of parkin substrates are therefore believed to lead to neurodegeneration in Parkinson's disease. Here, we identify the PSD-95/Discs-large/Zona Occludens-1 (PDZ) protein PICK1 as a novel parkin substrate. We find that parkin binds PICK1 via a PDZ-mediated interaction, which predominantly promotes PICK1 monoubiquitination rather than polyubiquitination. Consistent with monoubiquitination and recent work implicating parkin in proteasome-independent pathways, parkin does not promote PICK1 degradation. However, parkin regulates the effects of PICK1 on one of its other PDZ partners, the acid-sensing ion channel (ASIC). Overexpression of wild-type, but not PDZ binding- or E3 ubiquitin-ligase-defective parkin abolishes the previously described, protein kinase C-induced, PICK1-dependent potentiation of ASIC2a currents in non-neuronal cells. Conversely, the loss of parkin in hippocampal neurons from parkin knockout mice unmasks prominent potentiation of native ASIC currents, which is normally suppressed by endogenous parkin in wild-type neurons. Given that ASIC channels contribute to excitotoxicity, our work provides a mechanism explaining how defects in parkin-mediated PICK1 monoubiquitination could enhance ASIC activity and thereby promote neurodegeneration in Parkinson's disease.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.