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https://hdl.handle.net/10316/100110
Título: | Aberrant hippocampal transmission and behavior in mice with a stargazin mutation linked to intellectual disability | Autor: | Caldeira, G. L. Inácio, A. Beltrão, N. Barreto, C. A. V. Rodrigues, M. V. Rondão, T. Macedo, R. Gouveia, R. P. Edfawy, M. Guedes, J. Cruz, B. Louros, S. R. Moreira, I. S. Peça, J. Carvalho, A. L. |
Data: | 7-Mar-2022 | Editora: | Springer Nature | Projeto: | UIDB/04539/2020 POCI-01-0145-FEDER-28541 POCI-01-0145- FEDER-016682 PTDC/QUI-OUT/32243/2017 CPCA/A0/7302/2020 CENTRO-01-0145-FEDER-000008:BrainHealth 2020 info:eu-repo/grantAgreement/FCT/SFRH/SFRH/BD/51962/2012/PT info:eu-repo/grantAgreement/FCT/POR_CENTRO/SFRH/BD/144881/2019/PT/Cerebellar dysfunction in neuropsychiatric disorders: insights from human mutations in Stargazin info:eu-repo/grantAgreement/FCT/POR_CENTRO/SFRH/BD/129236/2017/PT/STARGAZIN AS A REGULATOR OF M-CURRENTS IN THE CENTRAL NERVOUS SYSTEM info:eu-repo/grantAgreement/FCT/SFRH/SFRH/2FBD/2F51958/2F2012/PT info:eu-repo/grantAgreement/FCT/OE/SFRH/BD/145457/2019/PT/A computational approach to the structural and dynamical characterization of the ghrelin receptor function and mechanism info:eu-repo/grantAgreement/FCT/FARH/SFRH/BPD/122299/2016/PT/COGNITIVE DISORDERS AS DEFECTS IN SYNAPTIC FUNCTION: INSIGHT FROM HUMAN MUTATIONS IN THE CACNG2 GENE info:eu-repo/grantAgreement/FCT/POR_CENTRO/SFRH/BPD/120611/2016/PT/Dissecting the role of metabotropic glutamate receptor sorting proteins in autism spectrum disorders info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID/NEU/04539/2013/PT |
Título da revista, periódico, livro ou evento: | Molecular Psychiatry | Resumo: | Mutations linked to neurodevelopmental disorders, such as intellectual disability (ID), are frequently found in genes that encode for proteins of the excitatory synapse. Transmembrane AMPA receptor regulatory proteins (TARPs) are AMPA receptor auxiliary proteins that regulate crucial aspects of receptor function. Here, we investigate a mutant form of the TARP family member stargazin, described in an ID patient. Molecular dynamics analyses predicted that the ID-associated stargazin variant, V143L, weakens the overall interface of the AMPAR:stargazin complex and impairs the stability of the complex. Knock-in mice harboring the V143L stargazin mutation manifest cognitive and social deficits and hippocampal synaptic transmission defects, resembling phenotypes displayed by ID patients. In the hippocampus of stargazin V143L mice, CA1 neurons show impaired spine maturation, abnormal synaptic transmission and long-term potentiation specifically in basal dendrites, and synaptic ultrastructural alterations. These data suggest a causal role for mutated stargazin in the pathogenesis of ID and unveil a new role for stargazin in the development and function of hippocampal synapses. | URI: | https://hdl.handle.net/10316/100110 | ISSN: | 1359-4184 1476-5578 |
DOI: | 10.1038/s41380-022-01487-w | Direitos: | openAccess |
Aparece nas coleções: | I&D CNC - Artigos em Revistas Internacionais IIIUC - Artigos em Revistas Internacionais FCTUC Ciências da Vida - Artigos em Revistas Internacionais |
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s41380-022-01487-w.pdf | 4.04 MB | Adobe PDF | Ver/Abrir |
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