Current models of synaptic scaffolding in the post-synaptic density (PSD) depict a largely static structure of several proteins anchoring receptors to the cytoskeleton. However, increasing evidence suggests that many proteins in the postsynaptic complex are dynamically regulated. One such class of proteins is the SAPAPs. The SAPAPs are shown in models of glutamatergic synapses as simple linkers acting between receptor binding proteins and the actin cytoskeleton. However, the SAPAPs are known to bind to signaling proteins, and we have found that SAPAPs mRNA is highly localized in dendrites - both indications of a more dynamic role in regulating synaptic function and plasticity. We thus propose that SAPAP proteins function as dynamic regulators of synapses by shuttling signaling molecules in and out of the PSD. To test this hypothesis, we will investigate the dynamics of the SAPAP molecules at synapses and determine whether dendritic targeting of SAPAP3 mRNA controls the synaptic dynamics of SAPAPS protein. These studies will help us understand whether dynamic PSD constituents may regulate synaptic function and plasticity.
