Abnormal mGluR-mediated synaptic plasticity and autism-like behaviours in Gprasp2 mutant mice
| Autor: | João Peça, Mário Jorge da Silva Carvalho, Xian Gao, Pedro A. Ferreira, Ana L. Cardoso, Gladys L. Caldeira, Mariana Laranjo, Joana R. Guedes, Guoping Feng, Ana Luísa Carvalho, Dongqing Wang, Mohamed Edfawy, Marta I Pereira, Lara O. Franco |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Science Dendritic Spines Receptor Metabotropic Glutamate 5 General Physics and Astronomy 02 engineering and technology Neurotransmission Biology Hippocampus Synaptic Transmission General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Glutamatergic Memory mental disorders medicine Animals Autistic Disorder Receptor lcsh:Science Mice Knockout Multidisciplinary Neuronal Plasticity Behavior Animal Metabotropic glutamate receptor 5 Intracellular Signaling Peptides and Proteins General Chemistry 021001 nanoscience & nanotechnology medicine.disease Mice Mutant Strains Mice Inbred C57BL 030104 developmental biology Autism spectrum disorder Metabotropic glutamate receptor Synaptic plasticity Autism lcsh:Q 0210 nano-technology Neuroscience Gene Deletion |
| Zdroj: | Nature Communications, Vol 10, Iss 1, Pp 1-15 (2019) Nature Communications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-019-09382-9 |
| Popis: | 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 mGluR5 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. GPRASP2 plays a role in trafficking of GPCRs and mutations in this gene have been linked to neurodevelopmental disorders. Here the authors study the role of Gprasp2 in the CNS and show that it regulates the surface availability of mGluR5 receptors and that knockout mice for this protein show autistic-like behavioural abnormalities. |
| Databáze: | OpenAIRE |
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