Molecular anatomy of the postsynaptic density

The postsynaptic density (PSD) is a structure composed of both membranous and cytoplasmic proteins localized at the postsynaptic plasma membrane of excitatory synapses. Biochemical and molecular biological studies have identified a number of proteins present in the PSD. Glutamate receptors are important constituents of the PSD and membrane proteins involved in synaptic signal transduction and cell adhesion are also essential components. Scaffolding proteins containing multiple protein interaction motifs are thought to provide the framework of the PSD through their interactions with both membrane proteins and the cytoplasmic proteins. Among the cytoplasmic signaling molecules, calcium-calmodulin-dependent protein kinase II stands out as a major component of the PSD and its dynamic translocation to the PSD in response to neuronal activity is crucial in synaptic signal transduction. Recent advancements in molecular biological, structural and electrophysiological techniques have enabled us to directly measure the number, distribution and interactions of PSD molecules with high sensitivity and precision. In this review, I describe the structure and molecular composition of the PSD as well as the molecular interactions between the major constituents. This information will be combined with recent quantitative analyses of the PSD protein contents per synapse, in order to provide a current view of the PSD molecular architecture and its dynamics.