Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

PSD-95 (Postsynaptic Density Protein-95)

Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101786


Historical Background

Postsynaptic protein-95 (PSD-95), the major scaffolding and hub protein found in excitatory chemical synapses, was originally discovered in 1992 when Mary B. Kennedy et al. observed a protein containing a guanylate kinase domain with a similar sequence to the Drosophila discs large (Dlg) 1 tumor suppressor protein in the rat brain (Cho et al. 1992). During the 1990s, Kennedy and her research team found that PSD-95 resides in the postsynaptic density (PSD) fraction, where it performs its primary function: stabilizing and organizing the array situated beneath the postsynaptic membrane (Hunt et al. 1996) that contains different proteins, ion channels, and synaptic receptors to promote normal synaptic transmission and function (Kornau et al. 1995; Zhang et al. 1999). PSD-95 remains a target of high interest due to its involvement in the regulation of...

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This work was supported by grants from the Basal Center of Excellence in Aging and Regeneration (CONICYT-PFB 12/2007) and FONDECYT (No. 1160724) to N. C. Inestrosa. D. Vallejo was a postdoctoral fellow.


  1. Ampuero E, et al. Interfering of the Reelin/ApoER2/PSD95 signaling axis reactivates dendritogenesis of mature hippocampal neurons. J Cell Physiol. 2016. Available at: http://www.ncbi.nlm.nih.gov/pubmed/27653801
  2. Bianchetta MJ, et al. Cyclin-dependent kinase 5 regulates PSD-95 ubiquitination in neurons. J Neurosci Off J Soc Neurosci. 2011;31(33):12029–35.Google Scholar
  3. Bustos FJ, et al. PSD95 suppresses dendritic arbor development in mature hippocampal neurons by occluding the clustering of NR2B-NMDA receptors. PLoS ONE. 2014;9(4):e94037. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3976375&tool=pmcentrez&rendertype=abstractPubMedPubMedCentralGoogle Scholar
  4. Cho KO, Hunt CA, Kennedy MB. The rat brain postsynaptic density fraction contains a homolog of the Drosophila discs-large tumor suppressor protein. Neuron. 1992;9(5):929–42.Google Scholar
  5. Colledge M, et al. Ubiquitination regulates PSD-95 degradation and AMPA receptor surface expression. Neuron. 2003;40(3):595–607.PubMedPubMedCentralGoogle Scholar
  6. de Arce KP, et al. Synaptic clustering of PSD-95 is regulated by c-Abl through tyrosine phosphorylation. J Neurosci Off J Soc Neurosci. 2010;30(10):3728–38.Google Scholar
  7. El-Husseini AE, et al. PSD-95 involvement in maturation of excitatory synapses. Science (New York, NY). 2000;290(5495):1364–8.Google Scholar
  8. El-Husseini AED, et al. Synaptic strength regulated by palmitate cycling on PSD-95. Cell. 2002;108(6):849–63.Google Scholar
  9. Farías GG, et al. Wnt-5a/JNK signaling promotes the clustering of PSD-95 in hippocampal neurons. J Biol Chem. 2009;284(23):15857–66.PubMedPubMedCentralGoogle Scholar
  10. Gardoni F, et al. Calcium-calmodulin-dependent protein kinase II phosphorylation modulates PSD-95 binding to NMDA receptors. Eur J Neurosci. 2006;24(10):2694–704.Google Scholar
  11. Ho GPH, et al. S-nitrosylation and S-palmitoylation reciprocally regulate synaptic targeting of PSD-95. Neuron. 2011;71(1):131–41. Available at: http://dx.doi.org/10.1016/j.neuron.2011.05.033PubMedPubMedCentralGoogle Scholar
  12. Hunt CA, Schenker LJ, Kennedy MB. PSD-95 is associated with the postsynaptic density and not with the presynaptic membrane at forebrain synapses. J Neurosci Off J Soc Neurosci. 1996;16(4):1380–8.Google Scholar
  13. Kornau HC, et al. Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95. Science (New York, NY). 1995;269(5231):1737–40.Google Scholar
  14. Meyer D, Bonhoeffer T, Scheuss V. Balance and stability of synaptic structures during synaptic plasticity. Neuron. 2014;82(2):430–43. Available at: http://www.ncbi.nlm.nih.gov/pubmed/24742464PubMedGoogle Scholar
  15. Naisbitt S, et al. Interaction of the postsynaptic density-95/guanylate kinase domain-associated protein complex with a light chain of myosin-V and dynein. J Neurosci Off J Soc Neurosci. 2000;20(12):4524–34. Available at: http://www.ncbi.nlm.nih.gov/pubmed/10844022PubMedGoogle Scholar
  16. Nelson CD, et al. Phosphorylation of threonine-19 of PSD-95 by GSK-3β is required for PSD-95 mobilization and long-term depression. J Neurosci. 2013;33(29):12122–35. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3929687&tool=pmcentrez&rendertype=abstractPubMedPubMedCentralGoogle Scholar
  17. Sturgill JF, et al. Distinct domains within PSD-95 mediate synaptic incorporation, stabilization, and activity-dependent trafficking. J Neurosci Off J Soc Neurosci. 2009;29(41):12845–54.Google Scholar
  18. Takahashi H, et al. Drebrin-dependent actin clustering in dendritic filopodia governs synaptic targeting of postsynaptic density-95 and dendritic spine morphogenesis. J Neurosci Off J Soc Neurosci. 2003;23(16):6586–95. Available at: http://www.ncbi.nlm.nih.gov/pubmed/12878700PubMedGoogle Scholar
  19. Vallejo D, Codocedo JF, Inestrosa NC. Posttranslational modifications regulate the postsynaptic localization of PSD-95. Mol Neurobiol. 2016. Available at: http://link.springer.com/10.1007/s12035-016-9745-1
  20. Varela-Nallar L, et al. Wingless-type family member 5A (Wnt-5a) stimulates synaptic differentiation and function of glutamatergic synapses. Proc Natl Acad Sci U S A. 2010;107(49):21164–9.PubMedPubMedCentralGoogle Scholar
  21. Vogl AM, et al. Neddylation inhibition impairs spine development, destabilizes synapses and deteriorates cognition. Nat Neurosci. 2015;18(2):239–51. Available at: http://www.nature.com/doifinder/10.1038/nn.3912
  22. Zhang W, et al. Citron binds to PSD-95 at glutamatergic synapses on inhibitory neurons in the hippocampus. J Neurosci Off J Soc Neurosci. 1999;19(1):96–108. Available at: http://www.ncbi.nlm.nih.gov/pubmed/9870942PubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Centro de Envejecimiento y Regeneración (CARE), Departamento de Biología Celular y Molecular, Facultad de Ciencias BiológicasPontificia Universidad Católica de ChileSantiagoChile
  2. 2.Centro de Excelencia en Biomedicina de Magallanes (CEBIMA)Universidad de MagallanesPunta ArenasChile