Postsynaptic scaffolding protein

Impairment of synaptic plasticity underlies memory dysfunction in AD. Molecules involved in this plasticity such as PSD-95, a major postsynaptic scaffold protein at excitatory synapses, may play an important role in AD pathogenesis. Either A(1 or tau can induce reduction of PSD-95 in excitatory synapses in hippocampus. This PSD-95 reduction is not an early event but occurs as the pathologies advance. Thus, the time-dependent PSD-95 reduction from synapses and accumulation in neuronal soma in transgenic mice and Hirano bodies in AD may mark postsynaptic degeneration that underlies long-term functional deficits [80],... 

Saez ET, Pehar M, Vargas MR, Barbeito L, Maccioni RB (2006) Production of nerve growth factor by beta-amyloid-stimulated astrocytes induces p75NTR-dependent tau hyperphosphorylation in cultured hippocampal neurons. J Neurosci Res 84 1098-1106 Sala C, Roussignol G, Meldolesi J, Fagni L (2005) Key role of the postsynaptic density scaffold proteins Shank and Homer in the functional architecture of Ca homeostasis at dendritic spines in hippocampal neurons. J Neurosci 25 4587 592 Santello M, Volterra A (2008) Synaptic modulation by astrocytes via Ca(2-l-)-dependent glutamate release. Neuroscience 158 253-9... 

It is noteworthy that Src-induced increase in NR1-NR2A receptor activity is promoted by the coexpression of postsynaptic density protein known as PSD-95 [37]. PSD-95 is a scaffolding protein consisting of multiple protein-protein interaction domains - three N-terminal PDZ domains, an SH3 domain and a C-terminal guanyl-ate kinase domain. The first two PDZ domains interact with the NR2 C-terminal tails while the third PDZ domain... 

Sala, C., Roussignol, G., Meldolesi, J., and Fagni, L. (2005). Key role of the postsynaptic density scaffold proteins Shank and Homer in the functional architecture of Ca2+ homeostasis at dendritic spines in hippocampal neurons. J. Neurosci. 25, 4587-4592. 

Postsynaptic Density Scaffolding Proteins at Excitatory Synapse and Disorders of Synaptic Plasticity Implications for Human Behavior Pathologies... 

Anchoring to the subsynaptic cytoskeleton can be considered a final step in the process of postsynaptic targeting of glutamate receptors. By binding to cytoskeletal elements, a scaffold protein such as PSD-95 can indirectly connect NMDA receptors to the cytoskeleton. 

A neurally derived signaling protein, agrin, acts through a receptor tyrosine kinase, MuSK, in the formation of the specialized postsynaptic endplate by interaction with rapsyn. Thus, MuSK-rapsyn interactions are critical in forming the local scaffold for postsynaptic components in the motor endplate [43,44]. 

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