β-Arrestin2 Couples Metabotropic Glutamate Receptor 5 to Neuronal Protein Synthesis and Is a Potential Target to Treat Fragile X.

ABSTRACT: Synaptic protein synthesis is essential for modification of the brain by experience and is aberrant in several genetically defined disorders, notably fragile X (FX), a heritable cause of autism and intellectual disability. Neural activity directs local protein synthesis via activation of metabotropic glutamate receptor 5 (mGlu₅), yet how mGlu₅ couples to the intracellular signaling pathways that regulate mRNA translation is poorly understood. Here, we provide evidence that β-arrestin2 mediates mGlu₅-stimulated protein synthesis in the hippocampus and show that genetic reduction of β-arrestin2 corrects aberrant synaptic plasticity and cognition in the Fmr1^-/y mouse model of FX. Importantly, reducing β-arrestin2 does not induce psychotomimetic acti

SUBMITTER: Stoppel LJ 

PROVIDER: S-EPMC5391046 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature