Trends in Neurosciences
The postsynaptic density at glutamatergic synapses
Section snippets
What is the PSD fraction?
The PSD is a fibrous specialization of the submembrane cytoskeleton that adheres to the postsynaptic membrane in register with the active zones that are located in the presynaptic terminal. Several functions, including regulation of adhesion, control of receptor clustering, and regulation of receptor function have been proposed for this structure[1]. The PSD is especially prominent in excitatory CNS synapses[2] where it was first described as a Type-I or asymmetric PSD (3, 4). In the 1970s, two
New PSD proteins
The cytoskeletal proteins tubulin, actin and fodrin, and the signal-transduction protein calmodulin were identified in the first phase of biochemical work on proteins that are contained in the PSD fraction (reviewed in [19]). A protein band that had been termed the major PSD protein[11], was later identified as the a subunit of Ca2+–calmodulin kinase type II (CaMKII)20, 21, 22, 23. The identification of these proteins strengthened the original hypothesis that the function of the PSD might be to
The PSD-95 family
The first new core protein that was identified by cDNA cloning of proteins from the PSD fraction was termed PSD-95 by our laboratory[12], and SAP-90 (synapse-associated protein) by Kistner et al.[14] Its specific association with the Type-I PSD in forebrain synapses was verified by immunocytochemistry[16]. In the cerebellum, PSD-95 is found at unusual `septate' junctions that maintain the convoluted shape of the presynaptic terminal of basket cells termed the `pinceau'14, 16, 26. PSD-95 is an
Type-2 subunits of the NMDA receptor
The laboratory of James Gurd reported a number of years ago that a 180kDa glycoprotein in the PSD fraction, termed gp180, is phosphorylated by a tyrosine kinase activity present in the PSD fraction[48] and also by CaM kinase II ([49]). Because of our interest in identifying potential substrates for CaMKII in the PSD, we purified and sequenced individual bands in the PSD fraction that migrate with an apparent Mr of 180kDa. One prominent protein with an Mr of 180kDa was identified as the 2B
Densin-180
An additional glycoprotein that co-migrates with NR2B during electrophoresis in SDS-polyacrylamide gels of the PSD fraction has recently been extensively characterized and termed densin-180 ([8]). Densin-180 has many of the hallmarks of an adhesion molecule. It is strongly enriched in the PSD fraction compared with brain homogenates and synaptosomes and is highly concentrated at synaptic sites along dendrites in cultured hippocampal neurons, co-localizing with synapsin, a marker for presynaptic
Concluding remarks
Study of the proteins of the PSD fraction provides a unique and useful view of the glutamatergic synapse. It has already contributed to the characterization of at least one major mechanism of assembly of postsynaptic machinery, and promises to reveal others. The PSD is formed very early during synaptogenesis of the CNS ([60]). Little is known about its precise role in synaptogenesis or in the medically important process of regeneration. The identification of its molecular constituents will
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