Abnormal MGluR-mediated Synaptic Plasticity and Autism-like Behaviours in Gprasp2 Mutant Mice

Overview

Journal Nat Commun

Specialty Biology

Date 2019 Mar 31

PMID 30926797

Citations 29

Authors

Mohamed Edfawy

Joana R Guedes

Marta I Pereira

Mariana Laranjo

Mario J Carvalho

Xian Gao

Pedro A Ferreira

Gladys Caldeira

Lara O Franco

Dongqing Wang

Ana Luisa Cardoso

Guoping Feng

Ana Luisa Carvalho

Joao Peca

Affiliations

Soon will be listed here.

Abstract

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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