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

Mohamed Edfawy, Joana R. Guedes, Marta I. Pereira, Mariana Laranjo, Mário J. Carvalho, Xian Gao, Pedro A. Ferreira, Gladys Caldeira, Lara O. Franco, Dongqing Wang, Ana Luisa Cardoso, Guoping Feng, Ana Luisa Carvalho and João Peça ()
Additional contact information
Mohamed Edfawy: University of Coimbra
Joana R. Guedes: University of Coimbra
Marta I. Pereira: University of Coimbra
Mariana Laranjo: University of Coimbra
Mário J. Carvalho: University of Coimbra
Xian Gao: Massachusetts Institute of Technology
Pedro A. Ferreira: University of Coimbra
Gladys Caldeira: University of Coimbra
Lara O. Franco: University of Coimbra
Dongqing Wang: Massachusetts Institute of Technology
Ana Luisa Cardoso: University of Coimbra
Guoping Feng: Massachusetts Institute of Technology
Ana Luisa Carvalho: University of Coimbra
João Peça: University of Coimbra

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: 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 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.

Date: 2019
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-019-09382-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09382-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-09382-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().