{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Akande A"],"funding":["NIGMS NIH HHS","NIH HHS"],"pagination":["94"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12487352"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["22(1)"],"pubmed_abstract":["Neurogranin (Ng), a known regulator of neuronal Ca²⁺-calmodulin (CaM) signaling, is linked to Alzheimer's disease. Though well-studied in neurons, Ng is also expressed in brain vasculature, where its function remains unclear. To investigate Ng's role in brain microvascular endothelial cells, we defined its interactome using immunoprecipitation-mass spectrometry (IP-MS) under high- and low-Ca²⁺ conditions. Among 119 Ng-binding proteins, we discovered a novel interaction between Ng and MYH9, a key regulator of cytoskeletal remodeling. Ng-MYH9 binding was prominent in high Ca²⁺ and validated via CaM affinity pulldown and proximity ligation assays. Ng knockdown reduced F-actin levels, while MYH9 knockdown decreased both Ng and F-actin. Loss of Ng-MYH9 also impaired AKT-GSK3β signaling and elevated the endothelial activation marker VCAM1. Ng-null mice exhibited disrupted brain microvascular architecture and reduced MYH9 expression in endothelial cells. These findings reveal a novel Ng pathway promoting MYH9-dependent cytoskeletal remodeling and a potential role in maintaining blood-brain barrier integrity, a previously unrecognized function for Ng in brain health and Alzheimer's disease."],"journal":["Fluids and barriers of the CNS"],"pubmed_title":["Neurogranin-MYH9 interaction regulates cytoskeletal remodeling in cerebral vasculature."],"pmcid":["PMC12487352"],"funding_grant_id":["P20GM121307","P20 GM134974","P20 GM121307"],"pubmed_authors":["Park JE","Akande A","Scott R","Nam HW","Alexander JS"],"additional_accession":[]},"is_claimable":false,"name":"Neurogranin-MYH9 interaction regulates cytoskeletal remodeling in cerebral vasculature.","description":"Neurogranin (Ng), a known regulator of neuronal Ca²⁺-calmodulin (CaM) signaling, is linked to Alzheimer's disease. Though well-studied in neurons, Ng is also expressed in brain vasculature, where its function remains unclear. To investigate Ng's role in brain microvascular endothelial cells, we defined its interactome using immunoprecipitation-mass spectrometry (IP-MS) under high- and low-Ca²⁺ conditions. Among 119 Ng-binding proteins, we discovered a novel interaction between Ng and MYH9, a key regulator of cytoskeletal remodeling. Ng-MYH9 binding was prominent in high Ca²⁺ and validated via CaM affinity pulldown and proximity ligation assays. Ng knockdown reduced F-actin levels, while MYH9 knockdown decreased both Ng and F-actin. Loss of Ng-MYH9 also impaired AKT-GSK3β signaling and elevated the endothelial activation marker VCAM1. Ng-null mice exhibited disrupted brain microvascular architecture and reduced MYH9 expression in endothelial cells. These findings reveal a novel Ng pathway promoting MYH9-dependent cytoskeletal remodeling and a potential role in maintaining blood-brain barrier integrity, a previously unrecognized function for Ng in brain health and Alzheimer's disease.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Sep","modification":"2026-06-04T01:48:45.681Z","creation":"2026-05-04T03:13:57.996Z"},"accession":"S-EPMC12487352","cross_references":{"pubmed":["41029426"],"doi":["10.1186/s12987-025-00709-x"]}}