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 P(i) transporters carry out this task. Remarkably, the two families transport different P(i) species: whereas type II Na+/P(i) cotransporters (SCL34) prefer divalent HPO(4)(2-), type III Na(+)/P(i) cotransporters (SLC20) transport monovalent H2PO(4)(-). 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 P(i) homeostasis, and in salivary and mammary glands, liver, and testes they play a role in modulating the P(i) content 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 P(i) homeostasis; 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+/P(i) cotransporter families.