ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2018
USP8 Deubiquitinates SHANK3 to Control Synapse Density and SHANK3 Activity-Dependent Protein Levels.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- Review
- Elucidation of short linear motif-based interactions of the MIT and rhodanese domains of the ubiquitin-specific protease 8.Biology direct · 2025Article
- Neurodevelopmental Implications Underpinning Hereditary Spastic Paraplegia.CNS neuroscience & therapeutics · 2025Review
- Charting the shared genetic architecture of Alzheimer's disease, cognition, and educational attainment, and associations with brain development.Neurobiology of disease · 2024Article
- Post-ischemic ubiquitination at the postsynaptic density reversibly influences the activity of ischemia-relevant kinases.Communications biology · 2024Article
- The FGFR inhibitor Rogaratinib reduces microglia reactivity and synaptic loss in TBI.Frontiers in immunology · 2024Article
- Article
- Autism Spectrum Disorder: Neurodevelopmental Risk Factors, Biological Mechanism, and Precision Therapy.International journal of molecular sciences · 2023Review
- SHANK family on stem cell fate and development.Cell death & disease · 2022Review
- Article
- USP8 regulates liver cancer progression via the inhibition of TRAF6-mediated signal for NF-κB activation and autophagy induction by TLR4.Translational oncology · 2022Article
- SHANK3 Antibody Validation: Differential Performance in Western Blotting, Immunocyto- and Immunohistochemistry.Frontiers in synaptic neuroscience · 2022Article
- Historical perspective and progress on protein ubiquitination at glutamatergic synapses.Neuropharmacology · 2021Review
- Deubiquitylating enzymes in neuronal health and disease.Cell death & disease · 2021Review
- PCDH7 interacts with GluN1 and regulates dendritic spine morphology and synaptic function.Scientific reports · 2020Article
- Critical Roles of Deubiquitinating Enzymes in the Nervous System and Neurodegenerative Disorders.Molecules and cells · 2020Review
- The ubiquitin-editing enzyme A20 regulates synapse remodeling and efficacy.Brain research · 2020Article
- Network Structure Analysis Identifying Key Genes of Autism and Its Mechanism.Computational and mathematical methods in medicine · 2020Article
- USP8 Deubiquitinates the Leptin Receptor and Is Necessary for Leptin-Mediated Synapse Formation.Endocrinology · 2019Article
- Unexpected Compensatory Increase inFrontiers in molecular neuroscience · 2019Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations or altered protein levels of SHANK3 are implicated in neurodevelopmental disorders such as Phelan-McDermid syndrome, autism spectrum disorders, and schizophrenia (Guilmatre et al., 2014). Loss of SHANK3 in mouse models results in decreased synapse density and reduction in the levels of multiple synaptic proteins (Jiang and Ehlers, 2013). The family of SHANK scaffolding molecules are among the most heavily ubiquitinated proteins at the postsynaptic density. The ubiquitin-dependent proteasome degradation of SHANK is regulated by synaptic activity and may contribute to activity-dependent synaptic remodeling (Ehlers, 2003; Shin et al., 2012). However, the identity of the specific deubiquitinating enzymes and E3 ligases that regulate SHANK ubiquitination at synapses are unknown. Here we identify USP8/UBPY as a deubiquitinating enzyme that regulates SHANK3 and SHANK1 ubiquitination and protein levels. In primary rat neurons, USP8 enhances SHANK3 and SHANK1 protein levels via deubiquitination and increases dendritic spine density. Additionally, USP8 is essential for changes in SHANK3 protein levels following synaptic activity modulation. These data identify USP8 as a key modulator of SHANK3 downstream of synaptic activity.
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