Trends in Neurosciences
Volume 20, Issue 6, 1 June 1997, Pages 264-268
Journal home page for Trends in Neurosciences

The postsynaptic density at glutamatergic synapses

https://doi.org/10.1016/S0166-2236(96)01033-8Get rights and content

Abstract

The postsynaptic density (PSD) is a tiny, amorphous structure located beneath the postsynaptic membrane of synapses in the CNS. Until recently, the molecular composition and function of the PSD were mostly matters of speculation. With the advent of powerful new microchemical tools and molecular-genetic methods, three new classes of proteins have been identified in the PSD at glutamatergic synapses: the PSD-95 family, the NR2B subunit of the NMDA-type glutamate receptor, and densin-180. The PSD-95 family is involved in clustering of NMDA receptors. NR2B is phosphorylated by Ca2+–calmodulin-dependent protein kinase type II, a prominent constituent of the PSD. Densin-180 might represent a new class of synaptic adhesion molecule. Study of these molecules is beginning to reveal the functional significance of the PSD.

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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