Phosphate transporters: a tale of two solute carrier families

Abstract

Phosphate is an essential component of life and must be actively transported into cells against its electrochemical gradient. In vertebrates, two unrelated families of Na+-dependent Pitransporters carry out this task. Remarkably, the two families transport different Pispecies: whereas type II Na+/Picotransporters (SCL34) prefer divalent HPO42−, type III Na+/Picotransporters (SLC20) transport monovalent H2PO4−. The SCL34 family comprises both electrogenic and electroneutral members that are expressed in various epithelia and other polarized cells. Through regulated activity in apical membranes of the gut and kidney, they maintain body Pihomeostasis, and in salivary and mammary glands, liver, and testes they play a role in modulating the Picontent of luminal fluids. The two SLC20 family members PiT-1 and PiT-2 are electrogenic and ubiquitously expressed and may serve a housekeeping role for cell Pihomeostasis; however, also more specific roles are emerging for these transporters in, for example, bone mineralization. In this review, we focus on recent advances in the characterization of the transport kinetics, structure-function relationships, and physiological implications of having two distinct Na+/Picotransporter families.