Postsynaptic density (PSD) is a condensed protein-rich sub-compartment beneath the postsynaptic plasma membranes of each synapse. The PSD is responsible for receiving, amplifying, and storing signals begun by presynaptic cells. PSDs are made up of tightly packed proteins that form assemblies that are a few hundred nanometers wide and 30–50 nanometers thick (reviewed in 2015539).
Formation, Composition & dynamics (Assembly and disassembly)
Relation to human diseases
Proteome
Formation, Composition & dynamics (Assembly and disassembly)
PSDs are made up of hundreds of distinct proteins with varying abundances which are arranged as interconnected disc-shaped molecular assemblies. PSDs are notable for their dense assembly, which is attached to the postsynaptic plasma membranes on one side and exposed to the dendritic spine cytoplasm on the other. PSDs contain scaffold proteins such as PSD-9531, GKAP, Shank3, and Homer which undergo dynamic movements, forming distinct condensed nanoclusters. Therefore, the PSD assembly has key features of membraneless biological condensates. Proteins in PSDs are highly concentrated; PSD condensates can grow or shrink; components within the condensed PSDs are mobile and can exchange with corresponding molecules in the dilute cytoplasm of dendritic spines (reviewed in 32015539).
Relation to human diseases
The importance of PSDs in neurological diseases and neurodevelopmental disorders is intencely studied (12065602, 29415158, 28126896, 26317010, 23537733, 34504419).
Proteome
16507876 reported amlarge scale relative and absolute quantification of proteins in PSDs purified from adult rat forebrain and cerebellum.
29203896 documented the composition of postsynaptic proteomes in human neocortical regions.
30986977 developed targeted mass spectrometry-based approaches for quantitation of proteins nnriched in the PSD.
References
Chen X, Wu X, Wu H, Zhang M. Phase separation at the synapse. Nat Neurosci. 2020 Mar;23(3):301-310. doi: 10.1038/s41593-019-0579-9. Epub 2020 Feb 3. PMID: 32015539.
Chen X, Wu X, Wu H, Zhang M. Phase separation at the synapse. Nat Neurosci. 2020 Mar;23(3):301-310. doi: 10.1038/s41593-019-0579-9. Epub 2020 Feb 3. PMID: 32015539.
Boeckers TM, Bockmann J, Kreutz MR, Gundelfinger ED. ProSAP/Shank proteins - a family of higher order organizing molecules of the postsynaptic density with an emerging role in human neurological disease. J Neurochem. 2002 Jun;81(5):903-10. doi: 10.1046/j.1471-4159.2002.00931.x. PMID: 12065602.
Kaizuka T, Takumi T. Postsynaptic density proteins and their involvement in neurodevelopmental disorders. J Biochem. 2018 Jun 1;163(6):447-455. doi: 10.1093/jb/mvy022. PMID: 29415158.
Funk AJ, Mielnik CA, Koene R, Newburn E, Ramsey AJ, Lipska BK, McCullumsmith RE. Postsynaptic Density-95 Isoform Abnormalities in Schizophrenia. Schizophr Bull. 2017 Jul 1;43(4):891-899. doi: 10.1093/schbul/sbw173. PMID: 28126896; PMCID: PMC5472126.
Fourie C, Kim E, Waldvogel H, Wong JM, McGregor A, Faull RL, Montgomery JM. Differential Changes in Postsynaptic Density Proteins in Postmortem Huntington's Disease and Parkinson's Disease Human Brains. J Neurodegener Dis. 2014;2014:938530. doi: 10.1155/2014/938530. Epub 2014 Jan 16. PMID: 26317010; PMCID: PMC4437361.
Zhou J, Jones DR, Duong DM, Levey AI, Lah JJ, Peng J. Proteomic analysis of postsynaptic density in Alzheimer's disease. Clin Chim Acta. 2013 May;420:62-8. doi: 10.1016/j.cca.2013.03.016. Epub 2013 Mar 26. PMID: 23537733; PMCID: PMC3714371.
Wan L, Ai JQ, Yang C, Jiang J, Zhang QL, Luo ZH, Huang RJ, Tu T, Pan A, Tu E, Manavis J, Xiao B, Yan XX. Expression of the Excitatory Postsynaptic Scaffolding Protein, Shank3, in Human Brain: Effect of Age and Alzheimer's Disease. Front Aging Neurosci. 2021 Aug 24;13:717263. doi: 10.3389/fnagi.2021.717263. PMID: 34504419; PMCID: PMC8421777.
Cheng D, Hoogenraad CC, Rush J, Ramm E, Schlager MA, Duong DM, Xu P, Wijayawardana SR, Hanfelt J, Nakagawa T, Sheng M, Peng J. Relative and absolute quantification of postsynaptic density proteome isolated from rat forebrain and cerebellum. Mol Cell Proteomics. 2006 Jun;5(6):1158-70. doi: 10.1074/mcp.D500009-MCP200. Epub 2006 Feb 28. PMID: 16507876.
Roy M, Sorokina O, Skene N, Simonnet C, Mazzo F, Zwart R, Sher E, Smith C, Armstrong JD, Grant SGN. Proteomic analysis of postsynaptic proteins in regions of the human neocortex. Nat Neurosci. 2018 Jan;21(1):130-138. doi: 10.1038/s41593-017-0025-9. Epub 2017 Dec 4. PMID: 29203896.
Wilson RS, Rauniyar N, Sakaue F, Lam TT, Williams KR, Nairn AC. Development of Targeted Mass Spectrometry-Based Approaches for Quantitation of Proteins Enriched in the Postsynaptic Density (PSD). Proteomes. 2019 Apr 2;7(2):12. doi: 10.3390/proteomes7020012. PMID: 30986977; PMCID: PMC6630806.