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Abnormal mGluR-mediated synaptic plasticity and autism-like behaviours in Gprasp2 mutant mice.

08:00 EDT 29th March 2019 | BioPortfolio

Summary of "Abnormal mGluR-mediated synaptic plasticity and autism-like behaviours in Gprasp2 mutant mice."

Autism spectrum disorder (ASD) is characterized by dysfunction in social interactions, stereotypical behaviours and high co-morbidity with intellectual disability. A variety of syndromic and non-syndromic neurodevelopmental disorders have been connected to alterations in metabotropic glutamate receptor (mGluR) signalling. These receptors contribute to synaptic plasticity, spine maturation and circuit development. Here, we investigate the physiological role of Gprasp2, a gene linked to neurodevelopmental disabilities and involved in the postendocytic sorting of G-protein-coupled receptors. We show that Gprasp2 deletion leads to ASD-like behaviour in mice and alterations in synaptic communication. Manipulating the levels of Gprasp2 bidirectionally modulates the surface availability of mGluR and produces alterations in dendritic complexity, spine density and synaptic maturation. Loss of Gprasp2 leads to enhanced hippocampal long-term depression, consistent with facilitated mGluR-dependent activation. These findings demonstrate a role for Gprasp2 in glutamatergic synapses and suggest a possible mechanism by which this gene is linked to neurodevelopmental diseases.

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Journal Details

This article was published in the following journal.

Name: Nature communications
ISSN: 2041-1723
Pages: 1431

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A neuronal protein consisting of three PDZ DOMAINS, an SH3 DOMAIN, and a C-terminal guanylate kinase-like region (see MAGUK PROTEINS). It localizes to the POST-SYNAPTIC DENSITY and associates with the cytoplasmic tail of NMDA RECEPTORS and SHAKER POTASSIUM CHANNELS, playing a critical role in NMDA receptor-mediated SYNAPTIC PLASTICITY.

Serine/threonine protein kinase responsible for various SKELETAL MUSCLE functions; HEART CONDUCTION SYSTEM activity; calcium HOMEOSTASIS; calcium uptake by SARCOPLASMIC RETICULUM and SYNAPTIC PLASTICITY. It is encoded by the DMPK gene and its abnormal EXPANDED TRINUCLEOTIDE REPEAT of CTG in the 3'-UTR is associated with MYOTONIC DYSTROPHY 1.

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Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate via direct electrical coupling with ELECTRICAL SYNAPSES. Several other non-synaptic chemical or electric signal transmitting processes occur via extracellular mediated interactions.

Cytoskeleton specialization at the cytoplasmic side of postsynaptic membrane in SYNAPSES. It is involved in neuronal signaling and NEURONAL PLASTICITY and comprised of GLUTAMATE RECEPTORS; scaffolding molecules (e.g., PSD95, PSD93), and other proteins (e.g., CaCMKII).

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