Role of actin in the organisation of brain postsynaptic densities

Brain synaptic junctions are marked by a prominent dense-staining structure, the postsynaptic density (PSD), embedded in the postsynaptic membrane. Isolated PSDs contain a complex mixture of proteins among which the most abundant are the alpha subunit of calcium/calmodulin-dependent kinase II (CaMK II alpha), the membrane cytoskeletal proteins actin and spectrin and receptors for both excitatory and inhibitory neurotransmitters. We have investigated the relationship of these proteins to the junctional structure by extracting isolated PSDs with lithium diiodosalicylate (LIS). This selectively solubilized actin and spectrin while other prominent PSD proteins, such as CaMK II alpha, the AMPA- and NMDA-type glutamate receptors and GABA receptors, were not extracted at all. Electron microscopy revealed that LIS treatment caused some fragmentation of PSDs but that their basic lattice-like structure remained intact. These observations suggest that PSD structure is organised at two levels; a core component containing CaMK II alpha and neurotransmitter receptors which we have previously described as the postsynaptic junctional lattice and a peripheral actin-associated component that draws the lattice components together into the complete PSD structure.