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Beschreibung

Disks large homolog 4 (UniProt P78352, also known as Postsynaptic density protein 95, PSD-95, SAP-90, SAP90, Synapse-associated protein 90) is encoded by the DLG4 (also known as PSD95) gene (Gene ID 1742) in human. PSD-95 belong to the family of membrane-associated guanylate kinases (MAGUKs), which also include PSD-93, SAP97 and SAP102. PSD95 is predominantly expressed in the hippocampus CA1 region and prefrontal cortex of the brain, where it localizes in a somatodendritic pattern in the post-synaptic membrane and in presynaptic axon terminals of inhibitory neurons. PDS-95 is the major scaffolding protein in the excitatory postsynaptic density (PSD) and a potent regulator of synaptic strength via interactions with a diverse PSD proteins, including NMDA receptors (NMDARs), AMPA receptor (AMPAR) complexes via Stargazin/TARP, adhesion molecules, as well as other scaffolding proteins, such as GKAP and Shank. PSD95 and neuronal nitric-oxide synthase (nNOS) interaction plays a role in maintaining hypersensitivity in acute and chronic pain. In addition, the assembly of the GluR6-PSD95-CaMKII complex is implicated as a majore signaling module that mediates injury induced by brain ischemia by facilitating GluR6 serine phosphorylation by CaMKII and the activation of JNK.