The Subcellular Organization of Cortactin in Hippocampus

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Abstract
Spines may undergo rapid, activity-dependent changes in shape and size, reflecting reorganization of the actin cytoskeleton. This remodeling is implicated in development and also in the late phase of long-term potentiation. However, the cellular mechanisms that convert activity into morphological change remain poorly understood, and little is known about the anatomical distribution of the actin-regulating proteins that mediate this remodeling. Using immunocytochemistry, we demonstrate here that cortactin (a protein implicated in actin filament nucleation, branching, and stabilization) is concentrated in hippocampal spines, where it colocalizes with F-actin. Cortactin has a Shank-binding domain; recent studies report that synaptic activity may trigger actin remodeling via this interaction with Shank. However, our immunogold electron microscopic data show that cortactin concentrates within the spine core, 100-150 nm away from the postsynaptic density (PSD); only a small fraction of the cortactin in spines lies adjacent to the PSD. These data suggest that the adult dendritic spine contains two functional pools of cortactin: a large pool in the spine core that may help to mediates changes in spine shape and a small synaptic pool that may modify the PSD in response to synaptic activity.