ArticleFluids and barriers of the CNS2025
Neurogranin-MYH9 interaction regulates cytoskeletal remodeling in cerebral vasculature.
Article in Fluids and barriers of the CNS, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Protein glycoxidation in neuropsychiatric disorders-from basic research to clinical practice.Redox biology · 2026Review
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5 authors.
Funding
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.
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