PSD95/A0013

Post-synaptic density 95 protein (PSD95), also known as synapse-associated protein 90 (SAP90) or A0013, is a scaffold protein that belongs to the membrane-associated guanylate kinase (MAGUK) family (PSD93, PSD95, SAP97, SAP102).

Post-synaptic density 95 protein (PSD95), also known as synapse-associated protein 90 (SAP90) or A0013, is a scaffold protein that belongs to the membrane-associated guanylate kinase (MAGUK) family (PSD93, PSD95, SAP97, SAP102). The protein is expressed with different intensity in 17 tissues. Alternative splicing produces three isoforms with different length of the N-terminal domain of the protein. In brain, PSD95 is located in the post-synaptic density (PSD) structure, requiring palmitoylation to be targeted there. The predicted 724 amino acid sequence contains three PDZ domains, a SH3 domain, and a guanylate kinase-homology domain that interact with receptors, ion channels and associated signaling proteins. It binds the cytoplasmic tail of N-methyl-D-aspartate receptor (NMDAR) subunits and couples the receptor to an intracellular signaling pathway. In hippocampal neurons in culture, over-expression of PSD95 enhances post-synaptic clustering and activity of glutamate receptors whereas knock-down of PSD95 diminishes excitatory synapse number and clustering of glutamate receptors. In the PSD95 mutant mice, the NMDAR-mediated synaptic plasticity is dramatically altered with strengthened long-term potentiation (LTP) and impaired learning.