SAP97

SAP97, short for synapse-associated protein 97, is a member of the membrane-associated guanylate kinase (MAGUK) family of scaffold proteins. In humans it is encoded by the DLG1 gene. SAP97 functions as a key organizer at glutamatergic synapses, helping assemble and stabilize receptor complexes and signaling molecules at the postsynaptic density to regulate synaptic strength and plasticity.

Structurally, SAP97 contains three PDZ domains, an SH3 domain, and a guanylate kinase (GK)-like domain, along with N-terminal regions that can vary due to alternative splicing. This modular architecture enables interactions with a range of synaptic partners, including neurotransmitter receptors and cell adhesion molecules.

Localization and function at the synapse involve binding to NMDA receptor subunits (such as NR2A and NR2B) through PDZ-mediated interactions and associating with AMPA receptors, thereby influencing receptor trafficking, clustering, and stabilization at the postsynaptic membrane. SAP97 participates in pathways that regulate receptor delivery during synaptic activity and contributes to processes underlying long-term potentiation and long-term depression. It is also involved in larger MAGUK signaling networks that link receptors to cytoskeletal and signaling components.

Gene expression and relevance: DLG1 is expressed in the brain, with broader expression in other tissues. SAP97’s exact contribution to synaptic function can vary with development and neuronal type.

Clinical notes: Altered expression or function of SAP97 has been explored in relation to neuropsychiatric and developmental disorders, reflecting broader evidence that MAGUK scaffold proteins modulate synaptic connectivity and plasticity; detailed disease mechanisms remain an area of ongoing research.