Abstract

Introduction

Materials & Methods

Results

Discussion & Conclusion

References

Discussion
Board

Nitric oxide (NO) produced by neuronal nitric oxide synthase (nNOS) is important for NMDA receptor-dependent neurotransmitter release, neurotoxicity, and cGMP elevations. The coupling of NMDA receptor mediated calcium influx and nNOS activation is postulated to be due to a physical coupling of the receptor and the enzyme by an intermediary adaptor protein, PSD95, through a unique PDZ-PDZ domain interaction between PSD95 and nNOS. Here, we report the indentification of a novel nNOS-associated protein, CAPON, which is highly enriched in the brain and has numerous colocalizations with nNOS. CAPON interacts with the nNOS PDZ domain through its C terminus. CAPON competes with PSD95 for interaction with nNOS, and overexpression of CAPON results in a loss of PSD95/nNOS complexes in transfected cells. CAPON has a phosphotyrosine-binding domain in its N terminus. Here we also describe the purification of a PTB-binding protein which is enriched in synaptic vesicles. CAPON binds to this protein and nNOS is coupled to synaptic vesicles by this ternary interaction. The binding of nNOS to synaptic vesicles through CAPON may account for the highly potent effect of endogenously produced NO on synaptic vesicle release.

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Presentation Number SAjaffrey0890
Keywords: Synapse, PSD95, PDZ domain, subcellular local, neurotransmitter