Enlightening the postsynaptic density

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The postsynaptic density (PSD) is a specialization of the cytoskeleton at the synaptic junction. It lies adjacent to the cytoplasmic face of the postsynaptic membrane, in close apposition to the active zone of the synapse and the docked synaptic vesicles in the presynaptic terminal. Emerging evidence indicates that the PSD provides multiple functions and is an essential component of an extraordinary synaptic signaling assemblage. The PSD forms a disc that consists of cytoskeletal and regulatory proteins, some of which contact the cytoplasmic domains of ion channels in the postsynaptic membrane. This location places the PSD directly in the path of the intracellular ionic fluxes and second messenger cascades generated by neurotransmitters. It is now apparent that the PSD provides a structural matrix, which clusters ion channels in the postsynaptic membrane (reviewed by 73 , 75 and 34 and anchors signaling molecules such as kinases and phosphatases at the synapse (reviewed by Klauck and Scott 1995 ). These properties suggest that the PSD serves as a general organizer of the postsynaptic signal transduction machinery, which links regulatory molecules to their targets, coordinates developmental and activity-dependent changes in postsynaptic structures, and establishes the functional topography of the postsynaptic membrane. Important mechanisms for synaptic regulation, including long-term potentiation (LTP) and long-term depression (LTD), are likely to have a basis in the PSD. For example, a major component of the PSD, the α subunit of the Ca 2+ /calmodulin-dependent protein kinase II (αCaMKII; 76 , 49 and 72 has a central role in a current model for long-term memory 113 and 103 ). The NMDA receptor, which is required for several forms of synaptic plasticity (reviewed by Wilson and Tonegawa 1997 is clustered at the synapse by components of the PSD (reviewed by Sheng and Kim 1996 ). Thus, the PSD contributes to critical features of synaptic integration and regulation. Morphology of the PSD Junctional structures of neurons were first detected by the electron microscope in the 1950s as electron-dense specializations of pre- and postsynaptic membranes at the neuromuscular junction and at points of contact between cortical neurons at chemically transmitting synapses 28 and 122 ). In 1958, Palay observed that facing the nerve terminal, the opposite postsynaptic membrane is thickened and denser than it is elsewhere. This highly differentiated structure, shown for hippocampal CA1 and Purkinje cell synapses in Figure 1 , was called variously the postsynaptic thickening, the postsynaptic web, or the postsynaptic density. Typical PSDs are observed at type 1 glutamatergic excitatory synapses and are the focus of this review. A somewhat different PSD is seen at type 2 GABAergic and glycinergic inhibitory synapses 52 , 25 , 96 , 98 and 127 ). Related structures are also found at the neuromuscular junction Sanes 1997 ). Major morphological variants of type 1 synapses include axodendritic synaptic junctions formed on dendritic shafts, nonperforated axospinous synapses with a continuous PSD, and perforated synapses with a segmented PSD Peters et al. 1991 ).




Ziff, E. B. (1997). Enlightening the postsynaptic density. Neuron. Cell Press. https://doi.org/10.1016/S0896-6273(00)80409-2

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