Molecular Control of Growth-Related Sodium-Phosphate Co-transporter (SLC34A3)

The type IIa sodium-dependent inorganic phosphate transporter (NaPi-IIa) has a central regulatory role in inorganic phosphate (P i ) homeostasis. Many studies have reported on the functions and regulatory mechanisms of NaPi-IIa. NaPi-IIc, however, was initially identified as a NaPi transporter required for growth in rodents. The gene encoding NaPi-IIc is causative for hereditary hypophosphatemic rickets with hypercalciuria and considered to be a critical NaPi transporter in the human kidney. However, the physiological roles and regulatory mechanisms of NaPi-IIc are not sufficiently elucidated. Recent studies show that NaPi-IIc is tightly regulated by a variety of agonists and physiological conditions via partially defined molecular mechanisms, including transcriptional and posttranscriptional regulation, protein phosphorylation, trafficking (endocytosis, exocytosis, and recycling), and the association of NaPi-IIc with interacting protein complexes. These data provide further information about understanding of human renal P i handling. Here, we review recent findings regarding the molecular control of NaPi-IIc transporters.