SAP90 BINDS AND CLUSTERS KAINATE RECEPTORS CAUSING INCOMPLETE DESENSITIZATION

The mechanism of kainate receptor targeting and clustering is still un resolved. Here, we demonstrate that members of the SAP90/PSD-95 family colocalize and associate with kainate receptors. SAP90 and SAP102 coi mmunoprecipitate with both KA2 and GluR6, but only SAP97 coimmunopreci pitates with GluR6. Similar to NMDA receptors, GluR6 clustering is med iated by the interaction of its C-terminal amino acid sequence, ETMA, with the PDZ1 domain of SAP90. in contrast, the KA2 C-terminal region binds to, and is clustered by, the SH3 and GK domains of SAP90. Finall y, we show that SAP90 coexpressed with GluR6 or GluR6/KA2 receptors al ters receptor function by reducing desensitization. These studies sugg est that the organization and electrophysiological properties of synap tic kainate receptors are modified by association with members of the SAP90/PSD-95 family.