Overview
- Peptide (C)KDWGSSSGSQGRED, corresponding to amino acid residues 505-518 of human PSD-95 (Accession P78352). Intracellular, between the SH3 and the GK-like domains.
- Western blot analysis of rat (lanes 1 and 3) and mouse (lanes 2 and 4) brain membranes:1-2. Guinea Pig Anti-PSD-95 Antibody (#APZ-009-GP), (1:200).
3-4. Guinea Pig Anti-PSD-95 Antibody, preincubated with PSD-95 Blocking Peptide (BLP-PZ009).
The postsynaptic density (PSD) is a membrane-associated protein specialized in postsynaptic signal transduction and processing. There are four PSD family members classified according to their molecular weight, including, PSD-95, PSD-93, synaptic associated proteins 97 kDa and 102 kDa. PSD-95 interacts with both ionotropic and metabotropic glutamate receptors via protein–protein interactions and plays a role in their precise assembly and spatial organization as well as coupling of these receptors to downstream signaling events1.
PSD-95 contains a SH3 domain, a GK domain and three PDZ domains. The PDZ domains 1 and 2 of PSD-95 are separated by only a few residues, creating a rigid bond that may restrain interdomain flexibility. These two PDZ domains can have distinct or overlapping target-binding proteins. In contrast, PDZ3 of PSD-95 is located at the carboxyl terminal end of the protein and has a set of interacting proteins that are distinct from PDZ domains 1 and 2. The N-palmitoylation of PSD-95 at Cys-3 and Cys-5 residues is essential for enhanced synaptic responses and the trafficking of PSD-95 to the plasma membrane2. With its numerous domains, PSD-95 is often referred to as a scaffold protein, which localizes and traffics various receptors, cell adhesion molecules, ion channels, kinases and phosphatases to the synaptic membrane. PSD-95 also interacts with a variety of adaptor and cytoskeleton proteins, molecular motors, as well as protein synthesis machinery3.
PSD-95 is found at the postsynaptic membrane of excitatory synapses4.
PSD-95 null mice have severe learning defects and exhibit both facilitation of long-term potentiation and disruption of long-term depression5.