SAP97 promotes the stability of Na_x 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. Structured summary of protein interactions: Nax physically interacts with SAP97 by anti tag coimmunoprecipitation (View interaction) CNRasGEF binds to Nax by protein array (View interaction) Nax and SAP97 colocalize by fluorescence microscopy (View interaction) GIPC1 binds to Nax by protein array (View interaction) ZO-1 binds to Nax by protein array (View interaction) SAP97 binds to Nax by protein array (View interaction) Densin-180 binds to Nax by protein array (View interaction) Beta-1-syntrophin binds to Nax by protein array (View interaction) ERBIN binds to Nax by protein array (View interaction) Nax physically interacts with SAP97 by pull down (View interaction) Lnx1 binds to Nax by protein array (View interaction) nNOS binds to Nax by protein array (View interaction)