Abnormal mGluR-mediated synaptic plasticity and autism-like behaviours in Gprasp2 mutant mice
© 2019, The Author(s). 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 meta...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Science and Business Media LLC
2021
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| Online Access: | https://hdl.handle.net/1721.1/135042 |
| _version_ | 1811091293511614464 |
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| author | Edfawy, Mohamed Guedes, Joana R Pereira, Marta I Laranjo, Mariana Carvalho, Mário J Gao, Xian Ferreira, Pedro A Caldeira, Gladys Franco, Lara O Wang, Dongqing Cardoso, Ana Luisa Feng, Guoping Carvalho, Ana Luisa Peça, João |
| author_facet | Edfawy, Mohamed Guedes, Joana R Pereira, Marta I Laranjo, Mariana Carvalho, Mário J Gao, Xian Ferreira, Pedro A Caldeira, Gladys Franco, Lara O Wang, Dongqing Cardoso, Ana Luisa Feng, Guoping Carvalho, Ana Luisa Peça, João |
| author_sort | Edfawy, Mohamed |
| collection | MIT |
| description | © 2019, The Author(s). 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 5 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. |
| first_indexed | 2024-09-23T15:00:12Z |
| format | Article |
| id | mit-1721.1/135042 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T15:00:12Z |
| publishDate | 2021 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1350422022-03-30T14:32:47Z Abnormal mGluR-mediated synaptic plasticity and autism-like behaviours in Gprasp2 mutant mice Edfawy, Mohamed Guedes, Joana R Pereira, Marta I Laranjo, Mariana Carvalho, Mário J Gao, Xian Ferreira, Pedro A Caldeira, Gladys Franco, Lara O Wang, Dongqing Cardoso, Ana Luisa Feng, Guoping Carvalho, Ana Luisa Peça, João © 2019, The Author(s). 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 5 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. 2021-10-27T20:10:28Z 2021-10-27T20:10:28Z 2019 2019-07-18T13:55:13Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/135042 en 10.1038/s41467-019-09382-9 Nature Communications Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Springer Science and Business Media LLC Nature |
| spellingShingle | Edfawy, Mohamed Guedes, Joana R Pereira, Marta I Laranjo, Mariana Carvalho, Mário J Gao, Xian Ferreira, Pedro A Caldeira, Gladys Franco, Lara O Wang, Dongqing Cardoso, Ana Luisa Feng, Guoping Carvalho, Ana Luisa Peça, João Abnormal mGluR-mediated synaptic plasticity and autism-like behaviours in Gprasp2 mutant mice |
| title | Abnormal mGluR-mediated synaptic plasticity and autism-like behaviours in Gprasp2 mutant mice |
| title_full | Abnormal mGluR-mediated synaptic plasticity and autism-like behaviours in Gprasp2 mutant mice |
| title_fullStr | Abnormal mGluR-mediated synaptic plasticity and autism-like behaviours in Gprasp2 mutant mice |
| title_full_unstemmed | Abnormal mGluR-mediated synaptic plasticity and autism-like behaviours in Gprasp2 mutant mice |
| title_short | Abnormal mGluR-mediated synaptic plasticity and autism-like behaviours in Gprasp2 mutant mice |
| title_sort | abnormal mglur mediated synaptic plasticity and autism like behaviours in gprasp2 mutant mice |
| url | https://hdl.handle.net/1721.1/135042 |
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