An N-terminal and ankyrin repeat domain interactome of Shank3 identifies the protein complex with the splicing regulator Nono in mice.
SH3 and ankyrin‐repeat domain containing 3 (Shank3)
alternative splicing
autism spectrum disorder (ASD)
interaction
Journal
Genes to cells : devoted to molecular & cellular mechanisms
ISSN: 1365-2443
Titre abrégé: Genes Cells
Pays: England
ID NLM: 9607379
Informations de publication
Date de publication:
04 Jul 2024
04 Jul 2024
Historique:
revised:
17
06
2024
received:
05
04
2023
accepted:
20
06
2024
medline:
5
7
2024
pubmed:
5
7
2024
entrez:
4
7
2024
Statut:
aheadofprint
Résumé
An autism-associated gene Shank3 encodes multiple splicing isoforms, Shank3a-f. We have recently reported that Shank3a/b-knockout mice were more susceptible to kainic acid-induced seizures than wild-type mice at 4 weeks of age. Little is known, however, about how the N-terminal and ankyrin repeat domains (NT-Ank) of Shank3a/b regulate multiple molecular signals in the developing brain. To explore the functional roles of Shank3a/b, we performed a mass spectrometry-based proteomic search for proteins interacting with GFP-tagged NT-Ank. In this study, NT-Ank was predicted to form a variety of complexes with a total of 348 proteins, in which RNA-binding (n = 102), spliceosome (n = 22), and ribosome-associated molecules (n = 9) were significantly enriched. Among them, an X-linked intellectual disability-associated protein, Nono, was identified as a NT-Ank-binding protein. Coimmunoprecipitation assays validated the interaction of Shank3 with Nono in the mouse brain. In agreement with these data, the thalamus of Shank3a/b-knockout mice aberrantly expressed splicing isoforms of autism-associated genes, Nrxn1 and Eif4G1, before and after seizures with kainic acid treatment. These data indicate that Shank3 interacts with multiple RNA-binding proteins in the postnatal brain, thereby regulating the homeostatic expression of splicing isoforms for autism-associated genes after birth.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Japan Society for the Promotion of Science
ID : JP21K07865
Organisme : Japan Society for the Promotion of Science
ID : JP23K07334
Organisme : Japan Agency for Medical Research and Development
ID : JP20ek0109411
Organisme : Japan Agency for Medical Research and Development
ID : JP20wm0325002h
Organisme : The Ministry of Health, Labour and Welfare of Japan
ID : JP20FC1054
Organisme : The Ministry of Health, Labour and Welfare of Japan
ID : JP21FC1005
Informations de copyright
© 2024 The Author(s). Genes to Cells published by Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.
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