A de novo missense mutation in synaptotagmin-1 associated with neurodevelopmental disorder desynchronizes neurotransmitter release.
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
06 Feb 2024
06 Feb 2024
Historique:
received:
10
11
2022
accepted:
22
01
2024
revised:
12
01
2024
medline:
7
2
2024
pubmed:
7
2
2024
entrez:
6
2
2024
Statut:
aheadofprint
Résumé
Synaptotagmin-1 (Syt1) is a presynaptic calcium sensor with two calcium binding domains, C2A and C2B, that triggers action potential-induced synchronous neurotransmitter release, while suppressing asynchronous and spontaneous release. We identified a de novo missense mutation (P401L) in the C2B domain in a patient with developmental delay and autistic symptoms. Expressing the orthologous mouse mutant (P400L) in cultured Syt1 null mutant neurons revealed a reduction in dendrite outgrowth with a proportional reduction in synapses. This was not observed in single Syt1
Identifiants
pubmed: 38321119
doi: 10.1038/s41380-024-02444-5
pii: 10.1038/s41380-024-02444-5
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : ZonMw (Netherlands Organisation for Health Research and Development)
ID : 91216064
Organisme : ZonMw (Netherlands Organisation for Health Research and Development)
ID : 10250022110003
Organisme : ZonMw (Netherlands Organisation for Health Research and Development)
ID : 91216064
Organisme : ZonMw (Netherlands Organisation for Health Research and Development)
ID : 10250022110003
Organisme : Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research)
ID : 1160.18.200
Organisme : Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research)
ID : 1160.18.200
Informations de copyright
© 2024. The Author(s).
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