SAP97 promotes the stability of Nax channels at the plasma membrane.

Na(x) is a sodium-level sensor for body fluids expressed in the circumventricular organs in the brain. Na(x) has a putative PSD-95/Disc-large/ZO-1 (PDZ)-binding motif at the carboxyl (C)-terminus. Here we found that several PDZ proteins bind to Na(x) by PDZ-array overlay assay. Among them, synapse-associated protein 97 (SAP97/DLG1) was coexpressed with Na(x) in the subfornical organ. In C6 glioblastoma cells, destruction of the PDZ-binding motif of Na(x) or depletion of SAP97 resulted in a decrease in cell-surface Na(x), which was attenuated with inhibitors of endocytosis. These results indicate that SAP97 contributes to the stabilization of Na(x) channels at the plasma membrane.