Cortico-striatal synaptic defects and OCD-like behaviours in Sapap3-mutant mice.

Obsessive-compulsive disorder (OCD) is an anxiety-spectrum disorder characterized by persistent intrusive thoughts (obsessions) and repetitive actions (compulsions). Dysfunction of cortico-striato-thalamo-cortical circuitry is implicated in OCD, although the underlying pathogenic mechanisms are unknown. SAP90/PSD95-associated protein 3 (SAPAP3; also known as DLGAP3) is a postsynaptic scaffolding protein at excitatory synapses that is highly expressed in the striatum.

Differential mRNA expression and protein localization of the SAP90/PSD-95-associated proteins (SAPAPs) in the nervous system of the mouse.

The supramolecular anchoring/signaling complex at the postsynaptic density of glutamatergic synapses has been proposed to play a key role in regulating synaptic function and plasticity. One class of proteins present in the complex is the SAP90/PSD-95-associated protein family (SAPAPs). The SAPAPs, identified by their direct interaction with PSD-95 family proteins, were initially proposed to function in the anchoring/signaling complex as linker proteins between glutamate receptor binding proteins and the cytoskeleton.