ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
PKC phosphorylation regulates mGluR5 trafficking by enhancing binding of Siah-1A.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 45 citations in OpenAlex.
- The retinal light response is modulated by an mGluR5-mediated retrograde signal from ON-bipolar cells to photoreceptors.bioRxiv : the preprint server for biology · 2025Article
- Behavioral inflexibility through overtraining is mediated by reduced mGluR1/5 signaling capacity in the dorsolateral striatum.PLoS biology · 2025Article
- Ubiquitination of Metabotropic Glutamate Receptors and Associated Synaptic ProteinsJournal of cellular signaling · 2025Article
- mGluR5 from Primary Sensory Neurons Promotes Opioid-Induced Hyperalgesia and Tolerance by Interacting with and Potentiating Synaptic NMDA Receptors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Spinophilin Limits Metabotropic Glutamate Receptor 5 Scaffolding to the Postsynaptic Density and Cell Type Specifically Mediates Excessive Grooming.Biological psychiatry · 2023Article
- Prions induce an early Arc response and a subsequent reduction in mGluR5 in the hippocampus.Neurobiology of disease · 2022Article
- Historical perspective and progress on protein ubiquitination at glutamatergic synapses.Neuropharmacology · 2021Review
- Metabotropic glutamate receptor 5 inhibits α-synuclein-induced microglia inflammation to protect from neurotoxicity in Parkinson's disease.Journal of neuroinflammation · 2021Article
- Metabotropic Glutamate Receptor Trafficking and its Role in Drug-Induced Neurobehavioral Plasticity.Brain plasticity (Amsterdam, Netherlands) · 2021Review
- Host cell factors stimulate HIV-1 transcription by antagonizing substrate-binding function of Siah1 ubiquitin ligase to stabilize transcription elongation factor ELL2.Nucleic acids research · 2020Article
- Article
- Functional Cross-Talk between Adenosine and Metabotropic Glutamate Receptors.Current neuropharmacology · 2019Review
- The mGluR5 positive allosteric modulator VU0409551 improves synaptic plasticity and memory of a mouse model of Huntington's disease.Journal of neurochemistry · 2018Article
- Metabotropic glutamate receptor trafficking.Molecular and cellular neurosciences · 2018Review
- Ethanol-Induced Changes in PKCε: From Cell to Behavior.Frontiers in neuroscience · 2018Review
- Protein kinase Cɛ activity regulates mGluR5 surface expression in the rat nucleus accumbens.Journal of neuroscience research · 2017Article
- Sequences within the C Terminus of the Metabotropic Glutamate Receptor 5 (mGluR5) Are Responsible for Inner Nuclear Membrane Localization.The Journal of biological chemistry · 2017Article
- Organization and functions of mGlu and GABANature · 2016Review
- Metabotropic glutamate receptor subtype 5: molecular pharmacology, allosteric modulation and stimulus bias.British journal of pharmacology · 2016Review
- Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Glutamate is the major excitatory neurotransmitter in the mammalian CNS and acts on both ionotropic and metabotropic glutamate receptors (mGluRs). The mGluRs are widely distributed in the CNS and modulate a variety of neuronal processes, including neurotransmitter release and ion channel function. In hippocampus and cortex, mGluR5 is highly expressed and plays an important role in the regulation of synaptic plasticity. Calmodulin (CaM) binding dynamically regulates mGluR5 surface expression; however, the mechanisms linking CaM to mGluR5 trafficking are not clear. Recent studies showed that CaM binding to mGluR7 regulates its trafficking in a phosphorylation-dependent manner by disrupting the binding of protein interacting with C kinase 1. The E3 ligase seven in absentia homolog (Siah)-1A binds to mGluR5 and competes with CaM binding, making it an intriguing molecule to regulate phosphorylation-dependent trafficking of mGluR5. In the present study, we find that CaM competes with Siah-1A for mGluR5 binding in a phosphorylation-dependent manner in rat hippocampal neurons. Specifically, phosphorylation of mGluR5 S901 favors Siah-1A binding by displacing CaM. We identified critical residues regulating Siah-1A binding to mGluR5 and showed that binding is essential for the Siah-1A effects on mGluR5 trafficking. Siah-1A binding decreases mGluR5 surface expression and increases endosomal trafficking and lysosomal degradation of mGluR5. Thus CaM-regulated Siah-1A binding to mGluR5 dynamically regulates mGluR5 trafficking. These findings support a conserved role for CaM in regulating mGluR trafficking by PKC-dependent regulation of receptor-binding proteins.
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What OpenQuestion holds
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.