Publications by authors named "M J Grubisha"
Microtubule-associated protein 2 (MAP2) is a crucial regulator of dendritic structure and neuronal function, orchestrating diverse protein interactions within the microtubule network. We have shown MAP2 is hyperphosphorylated at serine 1782 (S1782) in schizophrenia and phosphomimetic mutation of S1782 in mice (MAP2) is sufficient to impair dendritic architecture. We sought to determine how this hyperphosphorylation affects the MAP2 interactome to provide insights into the disorder's mechanisms.
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- * Research reveals that the mutated PACS1 protein enhances its interaction with HDAC6, an enzyme, leading to reduced acetylation of certain neuronal proteins and negatively impacting neuron structure and function.
- * Treatment with targeting agents for PACS1 or HDAC6 shows promise in restoring normal neuronal features and improving synaptic transmission in affected brain areas, suggesting a potential therapeutic approach for PACS1 syndrome.
MAP2 is a critical cytoskeletal regulator in neurons. The phosphorylation of MAP2 (MAP2-P) is well known to regulate core functions of MAP2, including microtubule (MT)/actin binding and facilitation of tubulin polymerization. However, site-specific studies of MAP2-P function in regions outside of the MT-binding domain (MTBD) are lacking.
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- * A significant genetic factor is the PACS1 gene, where a specific mutation is associated with developmental delays and intellectual disabilities, but the mechanisms through which this occurs are not fully understood.
- * Research indicates that PACS1 interacts with the protein HDAC6, affecting the regulation of neuron structure and functioning; treatments targeting these proteins show promise in restoring normal neuronal function in models of PACS1 syndrome.