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Scaffolding Proteins of the Post-synaptic Density Contribute to Synaptic Plasticity by Regulating Receptor Localization and Distribution: Relevance for Neuropsychiatric Diseases
- Source :
- Neurochemical Research. 38:1-22
- Publication Year :
- 2012
- Publisher :
- Springer Science and Business Media LLC, 2012.
-
Abstract
- 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.
- Subjects :
- Nonsynaptic plasticity
Nerve Tissue Proteins
Neurotransmission
Biology
Biochemistry
Shank
Cellular and Molecular Neuroscience
Metaplasticity
Animals
Humans
PSD-95
Neuronal Plasticity
Synaptic scaling
Mental Disorders
Intracellular Signaling Peptides and Proteins
Membrane Proteins
Post-Synaptic Density
Long-term potentiation
General Medicine
Receptors, Neurotransmitter
Cell biology
Homer
Synaptic fatigue
NMDA
Synaptic plasticity
Schizophrenia
Nervous System Diseases
Glutamate
Disks Large Homolog 4 Protein
Neuroscience
Postsynaptic density
Subjects
Details
- ISSN :
- 15736903 and 03643190
- Volume :
- 38
- Database :
- OpenAIRE
- Journal :
- Neurochemical Research
- Accession number :
- edsair.doi.dedup.....c8c6b3b53fe363a3c7cd820a31d8b163