The SLC34 family of sodium-dependent phosphate transporters is a unique class of membrane transport proteins that share no obvious homology with the other solute carrier families, even at the bacterial level. It consists of three members, NaPiIIa (SLC34A1), NaPi-IIb (SLC34A2), and NaPi-IIc (SLC34A3), which mediate the translocation of divalent inorganic phosphate (HPO42-) together with two (NaPi-IIc) or three sodium ions (NaPi-IIa and NaPi-IIb), respectively. Therefore, phosphate transport by NaPi-IIa and NaPi-IIb is electrically produced. There is currently no 3-D structure of the mammalian SLC34 proteins or their bacterial homologs, so all structural information has been derived from indirect biophysical and biochemical studies on wild-type and engineered mutations.
Fig.1 Transport mechanism of SLC34 proteins. (Wagner, 2014)
NaPi-IIa and NaPi-IIc are mainly expressed in the brush border membrane of the proximal tubule, while NaPi-IIb is found in many more organs including liver, lung, the small intestine, and testis. The abundance and activity of these transporters are primarily regulated by changes in their expression on the cell surface and are determined by interactions with proteins involved in scaffolding, trafficking, or intracellular signaling. All three transporters are highly regulated by factors such as dietary phosphate status, hormones like parathyroid hormone, 1,25-OH2 vitamin D3 or FGF23, electrolyte, and acid-base status. The three members of the SLC34 family are associated with phosphaturia, hypophosphatemia, and ectopic organ calcifications.
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