title: Evolution of the Na-P(i) cotransport systems.
abstract: Membrane transport systems for P(i) transport are key elements in maintaining homeostasis of P(i) in organisms as diverse as bacteria and human. Two Na-P(i) cotransporter families with well-described functional properties in vertebrates, namely NaPi-II and NaPi-III, show conserved structural features with prokaryotic origin. A clear vertical relationship can be established among the mammalian protein family NaPi-III, a homologous system in C. elegans, the yeast system Pho89, and the bacterial P(i) transporter Pit. An alternative lineage connects the mammalian NaPi-II-related transporters with homologous proteins from Caenorhabditis elegans and Vibrio cholerae. The present review focuses on the molecular evolution of the NaPi-II protein family. Preliminary results indicate that the NaPi-II homologue cloned from V. cholerae is indeed a functional P(i) transporter when expressed in Xenopus oocytes. The closely related NaPi-II isoforms NaPi-IIa and NaPi-IIb are responsible for regulated epithelial Na-dependent P(i) transport in all vertebrates. Most species express two different NaPi-II proteins with the exception of the flounder and Xenopus laevis, which rely on only a single isoform. Using an RT-PCR-based approach with degenerate primers, we were able to identify NaPi-II-related mRNAs in a variety of vertebrates from different families. We hypothesize that the original NaPi-IIb-related gene was duplicated early in vertebrate development. The appearance of NaPi-IIa correlates with the development of the mammalian nephron.
authors.affiliation: Department of Physiological Sciences, University of Newcastle, Newcastle upon Tyne NE2 4HH, United Kingdom. andreas.werner@ncl.ac.uk
authors.forename: A
authors.initials: A
authors.lastname: Werner
authors.forename: R K
authors.initials: RK
authors.lastname: Kinne
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001419:Bacteria / Q000235:genetics; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D019143:Evolution, Molecular; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D050608:Sodium-Phosphate Cotransporter Proteins; D050611:Sodium-Phosphate Cotransporter Proteins, Type III; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa; D050614:Sodium-Phosphate Cotransporter Proteins, Type IIb; D027981:Symporters; D014714:Vertebrates; D014734:Vibrio cholerae / Q000235:genetics / Q000502:physiology
chemical_list: D002352:Carrier Proteins; C493567:PHO89 protein, S cerevisiae; C493554:SLC34A1 protein, human; C493557:SLC34A2 protein, human; D029701:Saccharomyces cerevisiae Proteins; D050608:Sodium-Phosphate Cotransporter Proteins; D050611:Sodium-Phosphate Cotransporter Proteins, Type III; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa; D050614:Sodium-Phosphate Cotransporter Proteins, Type IIb; D027981:Symporters