ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
Ubiquitination acutely regulates presynaptic neurotransmitter release in mammalian neurons.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 105 citations in OpenAlex.
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- Historical perspective and progress on protein ubiquitination at glutamatergic synapses.Neuropharmacology · 2021Review
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- The proteasome and its role in the nervous system.Cell chemical biology · 2021Review
- A Proteomic Approach for Systematic Mapping of Substrates of Human Deubiquitinating Enzymes.International journal of molecular sciences · 2021Article
- The Ubiquitinated Axon: Local Control of Axon Development and Function by Ubiquitin.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Review
- Autophagy and the endolysosomal system in presynaptic function.Cellular and molecular life sciences : CMLS · 2021Review
- Bassoon inhibits proteasome activity via interaction with PSMB4.Cellular and molecular life sciences : CMLS · 2021Article
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- The Ubiquitin Proteasome System in Neuromuscular Disorders: Moving Beyond Movement.International journal of molecular sciences · 2020Review
- The environmental toxicant ziram enhances neurotransmitter release and increases neuronal excitability via the EAG family of potassium channels.Neurobiology of disease · 2020Article
- Article
9 more citing papers are in PubMed but not listed here.
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2 authors at 1 institution in 1 country.
Funding
Abstract
The ubiquitin proteasome system (UPS) plays a crucial role in modulating synaptic physiology both presynaptically and postsynaptically, but the regulatory mechanisms remain obscure. To determine acute effects of proteasome inhibition on neurotransmission, we performed whole-cell voltage-clamp recordings from cultured rodent hippocampal neurons. We find that proteasome inhibitors induce a strikingly fast, severalfold increase in the frequency of both miniature (mini) and spontaneous synaptic currents at excitatory and inhibitory synapses. The lack of change in mini amplitude and kinetics indicates a presynaptic site of action. This effect does not depend on increased levels of presynaptic proteins, previously suggested as proteasomal targets. Furthermore, blockade of the UPS using E1-activating enzyme inhibitors also increases mini frequency, demonstrating that accumulation of ubiquitinated proteins is not required. Overall, these data suggest that the UPS not only orchestrates protein turnover, but also dynamically regulates the activity state of presynaptic proteins, thus crucially shaping synaptic transmission.
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Registered trials
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.