ArticleCell reports2015
Elevated CaMKIIα and Hyperphosphorylation of Homer Mediate Circuit Dysfunction in a Fragile X Syndrome Mouse Model.
Article in Cell reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
33 citing papers in PubMed, 57 citations in OpenAlex.
- Activity Deprivation Modulates the Shank3/Homer1/mGluR5 Signaling Pathway to Enable Synaptic Upscaling.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Therapeutic efficacy of the BKCa channel opener chlorzoxazone in a mouse model of Fragile X syndrome.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- SRC family kinase inhibition rescues molecular and behavioral phenotypes, but not protein interaction network dynamics, in a mouse model of Fragile X syndrome.Molecular psychiatry · 2024Article
- Female-specific dysfunction of sensory neocortical circuits in a mouse model of autism mediated by mGluR5 and estrogen receptor α.Cell reports · 2024Article
- Multiomics of early epileptogenesis in mice reveals phosphorylation and dephosphorylation-directed growth and synaptic weakening.iScience · 2024Article
- Preso enhances mGluR1-mediated excitotoxicity by modulating the phosphorylation of mGluR1-Homer1 complex and facilitating an ER stress after traumatic brain injury.Cell death discovery · 2024Article
- Growth-suppressor microRNAs mediate synaptic overgrowth and behavioral deficits in Fragile X mental retardation protein deficiency.iScience · 2024Article
- Article
- Article
- A perspective on molecular signalling dysfunction, its clinical relevance and therapeutics in autism spectrum disorder.Experimental brain research · 2022Review
- Review
- Activity dependent dissociation of the Homer1 interactome.Scientific reports · 2022Article
- Group I Metabotropic Glutamate Receptors and Interacting Partners: An Update.International journal of molecular sciences · 2022Review
- Restoring glutamate receptosome dynamics at synapses rescues autism-like deficits in Shank3-deficient mice.Molecular psychiatry · 2021Article
- Synaptic protein interaction networks encode experience by assuming stimulus-specific and brain-region-specific states.Cell reports · 2021Article
- The Complex Formed by Group I Metabotropic Glutamate Receptor (mGluR) and Homer1a Plays a Central Role in Metaplasticity and Homeostatic Synaptic Scaling.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Review
- Metabotropic Glutamate Receptor Trafficking and its Role in Drug-Induced Neurobehavioral Plasticity.Brain plasticity (Amsterdam, Netherlands) · 2021Review
- Novel roles of ER stress in repressing neural activity and seizures through Mdm2- and p53-dependent protein translation.PLoS genetics · 2019Article
- Activity-dependent changes in synaptic protein complex composition are consistent in different detergents despite differential solubility.Scientific reports · 2019Article
- Homer1a and mGluR1/5 Signaling in Homeostatic Sleep Drive and Output.The Yale journal of biology and medicine · 2019Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Abnormal metabotropic glutamate receptor 5 (mGluR5) function, as a result of disrupted scaffolding with its binding partner Homer, contributes to the pathophysiology of fragile X syndrome, a common inherited form of intellectual disability and autism caused by mutations in Fmr1. How loss of Fmr1 disrupts mGluR5-Homer scaffolds is unknown, and little is known about the dynamic regulation of mGluR5-Homer scaffolds in wild-type neurons. Here, we demonstrate that brief (minutes-long) elevations in neural activity cause CaMKIIα-mediated phosphorylation of long Homer proteins and dissociation from mGluR5 at synapses. In Fmr1 knockout (KO) cortex, Homers are hyperphosphorylated as a result of elevated CaMKIIα protein. Genetic or pharmacological inhibition of CaMKIIα or replacement of Homers with dephosphomimetics restores mGluR5-Homer scaffolds and multiple Fmr1 KO phenotypes, including circuit hyperexcitability and/or seizures. This work links translational control of an FMRP target mRNA, CaMKIIα, to the molecular-, cellular-, and circuit-level brain dysfunction in a complex neurodevelopmental disorder.
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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.