{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Classen J"],"funding":["European Research Council"],"pagination":["3181"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7035266"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["10(1)"],"pubmed_abstract":["Phosphorylation of Munc18-1 (Stxbp1), a presynaptic organizer of synaptic vesicle fusion, is a powerful mechanism to regulate synaptic strength. Munc18-1 is a proposed substrate for the Down Syndrome-related kinase dual-specificity tyrosine phosphorylation-regulate kinase 1a (Dyrk1a) and mutations in both genes cause intellectual disability. However, the functional consequences of Dyrk1a-dependent phosphorylation of Munc18-1 for synapse function are unknown. Here, we show that the proposed Munc18-1 phosphorylation site, T479, is among the highly constrained phosphorylation sites in the coding regions of the gene and is also located within a larger constrained coding region. We confirm that Dyrk1a phosphorylates Munc18-1 at T479. Patch-clamp physiology in conditional null mutant hippocampal"],"journal":["Scientific reports"],"pubmed_title":["A Munc18-1 mutant mimicking phosphorylation by Down Syndrome-related kinase Dyrk1a supports normal synaptic transmission and promotes recovery after intense activity."],"pmcid":["PMC7035266"],"funding_grant_id":["322966"],"pubmed_authors":["Meijer M","Sullivan PF","Classen J","Saarloos I","Verhage M"],"additional_accession":[]},"is_claimable":false,"name":"A Munc18-1 mutant mimicking phosphorylation by Down Syndrome-related kinase Dyrk1a supports normal synaptic transmission and promotes recovery after intense activity.","description":"Phosphorylation of Munc18-1 (Stxbp1), a presynaptic organizer of synaptic vesicle fusion, is a powerful mechanism to regulate synaptic strength. Munc18-1 is a proposed substrate for the Down Syndrome-related kinase dual-specificity tyrosine phosphorylation-regulate kinase 1a (Dyrk1a) and mutations in both genes cause intellectual disability. However, the functional consequences of Dyrk1a-dependent phosphorylation of Munc18-1 for synapse function are unknown. Here, we show that the proposed Munc18-1 phosphorylation site, T479, is among the highly constrained phosphorylation sites in the coding regions of the gene and is also located within a larger constrained coding region. We confirm that Dyrk1a phosphorylates Munc18-1 at T479. Patch-clamp physiology in conditional null mutant hippocampal","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Feb","modification":"2025-04-26T01:15:54.808Z","creation":"2020-05-22T11:20:40Z"},"accession":"S-EPMC7035266","cross_references":{"pubmed":["32081899"],"doi":["10.1038/s41598-020-59757-y"]}}