The Na-dependend Pi co-transporter NaPi-IIa is expressed in the brush border membrane (BBM) of renal proximal tubules. Its function is to reabsorb Pi from primary urine. Apical expression of NaPi-IIa is regulated by hormones and other factors such as availability of Pi. Regulation of NaPi-IIa is dependent on a network of protein-protein interactions in which NaPi-IIa is involved. By Yeast-Two-Hybrid screens PDZK2 and Gabarap were identified as NaPi-IIa interacting partners. Both proteins are involved in the regulation of either activity or expression of several membrane proteins.

Immunofluorescence on kidney cryosections revealed the presence of both proteins in the BBM of renal proximal tubules. Interactions between NaPi-IIa and both partners were confirmed by GST-Pull downs from BBM and transfected HEK293 cells. The PDZ-binding domain of NaPi-IIa (TRL) is critical for the interaction between NaPi-IIa and PDZK2. Preliminary data suggest that PDZK2 is a phosphoprotein.

In summary, we have confirmed the interaction of NaPi-IIa with PDZK2 and Gabarap in the context of proximal epithelia. Ongoing experiments will help to ascertain whether such interactions play a role in the adaptation of NaPi-IIa to changes on dietary Pi-intake.