Selective Disruption of Metabotropic Glutamate Receptor 5-Homer Interactions Mimics Phenotypes of Fragile X Syndrome in Mice.
Weirui GuoGemma MolinaroKatie A CollinsSeth A HaysRichard PaylorPaul F WorleyKaren K SzumlinskiKimberly M HuberPublished in: The Journal of neuroscience : the official journal of the Society for Neuroscience (2016)
Abnormal function of the metabotropic, or Gq-coupled, glutamate receptor 5 (mGlu5) has been implicated in neurodevelopmental disorders, including a genetic cause of intellectual disability and autism called fragile X syndrome. In brains of a mouse model of fragile X, mGlu5 is less associated with its binding partner Homer, a scaffolding protein that regulates mGlu5 localization to synapses and its ability to activate biochemical signaling pathways. Here we show that a mouse expressing a mutant mGlu5 that cannot bind to Homer is sufficient to mimic many of the biochemical, neurophysiological, and behavioral symptoms observed in the fragile X mouse. This work provides strong evidence that Homer-mGlu5 binding contributes to symptoms associated with neurodevelopmental disorders.
Keyphrases
- intellectual disability
- autism spectrum disorder
- mouse model
- binding protein
- signaling pathway
- wild type
- case report
- dna binding
- sleep quality
- metabolic syndrome
- depressive symptoms
- epithelial mesenchymal transition
- oxidative stress
- gene expression
- cell proliferation
- physical activity
- dna methylation
- adipose tissue
- transcription factor
- antiretroviral therapy