Project Summary

Jean-Claude Beique, Ph.D. (Young Investigator 2005) of Johns Hopkins University, proposes studying the role of the protein SAP102 in the regulation of the NMDA receptor, reduced function of which may lead to schizophrenia. The NMDA receptor is a receptor activated by synaptically released glutamate, the brain’s major excitatory neurotransmitter. But the molecular mechanism that controls the surface and synaptic expression of the NMDA receptor remains unclear. Some, though, propose that defects in these molecular processes, especially during synaptic developmental period, could contribute to the pathophysiology of schizophrenia. One protein potentially involved in regulating NMDA function is SAP102, which binds the receptor and regulates surface expression of the receptor. A recent study has reported reduced mRNA levels of SAP102 in the hippocampus of schizophrenic patients, but how SAP102 regulates NMDA receptor function is poorly understood. Dr. Beique aims to examine the interaction of SAP102 and NMDA by assessing the effects of SAP102 gene deletion on several determinants of synaptic transmission. A better understanding of the SAP102-NMDA receptor interaction may lead to the identification of novel targets to therapeutically modulate NMDA receptor function.

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS\Schizophrenia\Molecular

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