Using mass spectroscopy, we identified specific phosphorylation sites as key regulators of MAP2 function. Phosphorylation at these sites relocalizes MAP2 from microtubules to the actin cytoskeleton. Furthermore, we uncovered a potential new function for MAP2 as a scaffolding protein, suggesting that MAP2 not only organizes cytoskeletal proteins but also binds signaling molecules in a phosphorylation-dependent manner. In other studies, we are exploring the signal transduction pathways that control MAP2 phosphorylation and localization in vivo. A second project focuses on the regulation of dendritic spines.
Spines are specialized structures at synapses.
We found that actin filaments are crucial elements in the stability of dendritic spines and that the calcium-dependent protein phosphatase calcineurin participates in regulating the integrity of these actin filaments. Furthermore, in collaboration with other researchers at TSRI, we showed that dynamic actin filaments are critically involved in long-term potentiation. Several diseases of the nervous system, including mental retardation and Alzheimer's disease, and even normal aging are associated with abnormalities in the shape and density of dendritic spines and dendrites. Our ultimate goal is to understand how extracellular signals control neuronal morphology in both the normal and diseased nervous system. Smart, F.M., Halpain, S. Regulation of dendritic spine stability.