The sodium phosphate cotransporter family SLC34

Abstract

This review summarizes the characteristics of the solute carrier family SLC34 that is represented by the type ll Na/P(i)-cotransporters NaPi-lla (SLC34A1), NaPi-llb (SLC34A2) and NaPi-llc (SLC34A3). Other Na/P(i)-cotransporters are described within the SLC17 and SLC20 families. Type ll Na/P(i)-cotransporters are expressed in several tissues and play a major role in the homeostasis of inorganic phosphate. In kidney and small intestine, type ll Na/P(i)-cotransporters are located at the apical sites of epithelial cells and represent the rate limiting steps for transepithelial movement of phosphate. Physiological and pathophysiological regulation of renal and small intestinal epithelial transport of phosphate occurs through alterations in the abundance of type ll Na/P(i)-cotransporters.

Acid-Base Transport by the Renal Proximal Tubule

“…With Hediger, Romero generated a cDNA library from the salamander mRNA and methodically searched through ever-smaller groups of clones to arrive at a single clone that can serve as the template for cRNA that encodes the protein that we named NBC, for Na ϩ bicarbonate co-transporter (60). We anticipated that NBC could be genetically related to any of several known transporters, including the Na/glutamate transporters (subsequently grouped as part of the SLC1 family of solute-linked carriers [61]), the Cl-HCO 3 exchangers AE1 through 3 (now part of the SLC4 family [11]), the Na/monocarboxylate co-transporters (which turned out to be part of the SLC5 family that includes the Na/glucose co-transporters [62]), the Na/bile-salt transporters (SLC10 [63]), the cation-coupled Cl Ϫ co-transporters such as the Na/Cl co-transporter (SLC12 family [64]), the Na/carboxylate co-transporters (SLC13 [65]), and the Na/phosphate co-transporters (SLC17 and SLC34 [66,67]). Upon sequencing the cDNA clone that encodes NBC, we were surprised to learn that the deduced amino-acid sequence of salamander NBC is approximately 30% identical to that for the three anion exchangers AE1 though AE3, which group closely in the dendrogram in Figure 8 (blue region) and also are known as SLC4A1 through SLC4A3.…”

Intestinal and renal adaptation to a low-Pi diet of type II NaPi cotransporters in vitamin D receptor- and 1αOHase-deficient mice

“…IN SMALL INTESTINE AND RENAL proximal tubules, transepithelial transport of P i is initiated by members of the type II Na ϩ -dependent phosphate cotransporter family SLC34 (18), which are localized at the apical membrane of the respective epithelial cells. In adult mice, renal reabsorption of P i is determined largely by the abundance of NaP i type IIa (NaP i -IIa) in the brush-border membrane vesicles (BBMV) of proximal tubular cells and in small intestine by NaP i type IIb (NaP i -IIb), the only apical NaP i cotransporter known to be involved in the absorption of P i (14,19).…”

A Missense Mutation in the Sodium Phosphate Co-transporter Slc34a1 Impairs Phosphate Homeostasis

“…These transport proteins are specifically expressed in the brush border membranes of renal proximal tubules, where the bulk of filtered P i is reabsorbed, and mediate Na gradient-dependent transport of P i from primary urine to proximal tubular cells. 1 Regulation of Npt2a protein abundance in the apical membrane by factors such as dietary phosphate, parathyroid hormone, [2][3][4] and phosphatonins 5 occurs via the action of scaffolding proteins and protein kinases. 6,7 Inactivation of murine slc34a1 in mice led to a decrease in renal P i reabsorption arising from a defect in Na/P i co-transport.…”