The role of SAP97 in synaptic glutamate receptor dynamics

• DOI: 10.1073/pnas.0914422107
• Publication Date: 2010-02-04T03:10:32Z
• Authors: MacKenzie A. Howard; Guillermo M. Elias; Laura A. B. Elias; Wojciech Swat; Roger A. Nicoll
• Keywords: Guanylate kinase; Silent synapse

Proteins of the PSD-95-like membrane-associated guanylate kinase (PSD-MAGUK) family are vital for trafficking AMPA receptors (AMPARs) to synapses, a process necessary both basal synaptic transmission and forms plasticity. Synapse-associated protein 97 (SAP97) exhibits interactions, such as direct interaction with GluA1 AMPAR subunit, subcellular localization (synaptic, perisynaptic, dendritic) unique within this family. Due in part lethality germline knockout SAP97, protein's role plasticity is poorly understood. We found that overexpression SAP97 during early development traffics AMPARs NMDA (NMDARs) rescues deficits currents normally seen PSD-93/-95 double-knockout neurons. Mature neurons have experienced throughout exhibit enhanced NMDAR currents, well faster current decay kinetics. In loss-of-function experiments using conditional gene deletion, we recorded no glutamatergic or long-term potentiation. These results support hypothesis machinery glutamate compensates other PSD-MAGUKs mouse models. However, due functional redundancy, can presumably compensate when conditionally deleted development.