Bruneau_2009_FASEB.J_23_679

Changes in synaptic strength are important for synaptic development and synaptic plasticity. Most directly responsible for these synaptic changes are alterations in synaptic receptor number and density. Although alterations in receptor density mediated by the insertion, lateral mobility, removal, and recycling of receptors have been extensively studied, the dynamics and regulators of intracellular scaffolding proteins have only recently begun to be illuminated. In particular, a closer look at the receptor-associated proteins, which bind to receptors and are necessary for their synaptic localization and clustering, has revealed broader functions than previously thought and some rather unexpected thematic similarities. More than just "placeholders" or members of a passive protein "scaffold," receptor-associated proteins in every synapse studied have been shown to provide a number of signaling roles. In addition, the most recent state-of-the-art imaging has revealed that receptor-associated proteins are highly dynamic and are involved in regulating synaptic receptor density. Together, these results challenge the view that receptor-associated proteins are members of a static and stable scaffold and argue that their dynamic mobility may be essential for regulating activity-dependent changes in synaptic strength.