The SLC20 family of proteins: Dual functions as sodium-phosphate cotransporters and viral receptors

Abstract

The SLC20 family transport proteins were originally identified as retroviral receptors (called Glvr-1 and Ram-1). Since then, they have been shown to function as sodium-phosphate (Na/Pi) cotransporters, and have subsequently been classified as type III Na/Pi cotransporters (now called Pit-1 and Pit-2). The Pit cotransporters share ≈60% sequence homology, they have a high affinity for Pi, they are electrogenic with a coupling stoichiometry of >1 Na+ per Pi ion cotransported, and are inhibited by alkaline pH and phosphonoformic acid (PFA). Pit-1 and Pit-2 expression and/or activity has also been shown to be regulated by Pi deprivation in some, but not all cells and tissues examined. The Pit-1 and Pit-2 cotransporters are widely expressed, but cell-type specific expression has only been investigated in bone, kidney and intestine. Both proteins are likely expressed on the basolateral membranes of polarized epithelial cells, where they are likely involved in cellular Pi homeostasis. The Pit-1 and Pit-2 gene promoters have been cloned and characterized. While the exact roles of the Pit cotransporters in different cell types has not been definitively determined, they may be involved in important physiological pathways in bone, aortic smooth muscle cells, parathyroid glands, kidney and intestine.