2.A.58 The Phosphate:Na+ Symporter (PNaS) Family
The PNaS family includes several closely related, functionally characterized, sodium-dependent, inorganic phosphate (Pi) transporter (NPT2) proteins from mammals. Other animals, including fish and the worm, C. elegans, possess functionally uncharacterized homologues. One closely related bacterial protein, NptA of Vibrio cholerae, resembles the animal proteins to a much greater degree (34% identity; 51% similarity to many mammalian Npt2 symporters) than to any other bacterial homologue, and it may therefore have been obtained by lateral transfer from a eukaryotic source. Distantly related bacterial proteins are found in many bacteria including E. coli(543 aas; spP32683; 8 putative TMSs) and Bacillus subtilis(310 aas; spP54463; 8 putative TMSs). The bacterial homologue, NptA of V. cholerae has 10 putative TMSs. The well-characterized mammalian proteins are found in renal (IIa isoform) and intestinal (IIb isoform) brush border membranes and are about 640 amino acyl residues long with 8-12 putative TMSs. The N- and C-termini are in the cytoplasm, and a large hydrophilic loop is localized between TMSs 3 and 4. While IIa isoforms are pH-dependent, IIb isoforms are pH-independent (de la Horra et al., 2000).
Mammalian porters of the PNaS family may catalyze cotransport of 3 Na+ with inorganic phosphate. In response to parathyroid hormone and dietary inorganic phosphate, the renal cotransporter is rapidly inserted into and retrieved from the renal brush border membrane in a fashion similar to that by which the glucose transporter (Glut4) (2.A.1.1) is regulated by insulin and aquaporins 1 and 2 (1.A.8.1) are regulated by vasopressin (Levi et al., 1999). The renal type IIa PNaS member is a functional monomer (Kohler et al., 2001), but it interacts with PDZ proteins which probably mediate apical sorting, parathyroid hormone-controlled endocytosis and/or lysosomal sorting of internalized transporter (Gisler et al., 2001).
A single organism may have multiple paralogues of the PNaS family. All of these proteins exhibit an internal repeat that probably arose by a tandem intragenic duplication event. Their properties and mechanisms of action have been reviewed (Forster 2018).
The transport reaction catalyzed by the mammalian proteins is:
Pi (out) + 3 Na+ (out) ⇌ Pi (in) + 3 Na+ (in).