Neurochemical Research

, Volume 38, Issue 1, pp 1–22 | Cite as

Scaffolding Proteins of the Post-synaptic Density Contribute to Synaptic Plasticity by Regulating Receptor Localization and Distribution: Relevance for Neuropsychiatric Diseases

  • Felice Iasevoli
  • Carmine Tomasetti
  • Andrea de Bartolomeis


Synaptic plasticity represents the long lasting activity-related strengthening or weakening of synaptic transmission, whose well-characterized types are the long term potentiation and depression. Despite this classical definition, however, the molecular mechanisms by which synaptic plasticity may occur appear to be extremely complex and various. The post-synaptic density (PSD) of glutamatergic synapses is a major site for synaptic plasticity processes and alterations of PSD members have been recently implicated in neuropsychiatric diseases where an impairment of synaptic plasticity has also been reported. Among PSD members, scaffolding proteins have been demonstrated to bridge surface receptors with their intracellular effectors and to regulate receptors distribution and localization both at surface membranes and within the PSD. This review will focus on the molecular physiology and pathophysiology of synaptic plasticity processes, which are tuned by scaffolding PSD proteins and their close related partners, through the modulation of receptor localization and distribution at post-synaptic sites. We suggest that, by regulating both the compartmentalization of receptors along surface membrane and their degradation as well as by modulating receptor trafficking into the PSD, postsynaptic scaffolding proteins may contribute to form distinct signaling micro-domains, whose efficacy in transmitting synaptic signals depends on the dynamic stability of the scaffold, which in turn is provided by relative amounts and post-translational modifications of scaffolding members. The putative relevance for neuropsychiatric diseases and possible pathophysiological mechanisms are discussed in the last part of this work.


PSD-95 Shank Homer Glutamate Schizophrenia NMDA 


Conflict of interest

Authors declare they have no conflict of interest.


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© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Felice Iasevoli
    • 1
    • 2
  • Carmine Tomasetti
    • 1
  • Andrea de Bartolomeis
    • 1
  1. 1.Laboratory of Molecular Psychiatry and Psychopharmacotherapeutics, Section of Psychiatry, Department of NeuroscienceUniversity School of Medicine “Federico II”NaplesItaly
  2. 2.Department of NeuroscienceUniversity School of Naples “Federico II”NaplesItaly

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