Evolution of the Na-P-i cotransport systems

Membrane transport systems for P-i transport are key elements in maintainin g homeostasis of P-i in organisms as diverse as bacteria and human. Two Na- P-i cotransporter families with well-described functional properties in ver tebrates, namely NaPi-II and NaPi-III, show conserved structural features w ith prokaryotic origin. A clear vertical relationship can be established am ong the mammalian protein family NaPi-III, a homologous system in C. elegan s, the yeast system Pho89, and the bacterial P-i transporter Pit. An altern ative lineage connects the mammalian NaPi-II-related transporters with homo logous proteins from Caenorhabditis elegans and Vibrio cholerae. The presen t review focuses on the molecular evolution of the NaPi-II protein family. Preliminary results indicate that the NaPi-II homologue cloned from V. chol erae is indeed a functional Pi transporter when expressed in Xenopus oocyte s. The closely related NaPi-II isoforms NaPi-IIa and NaPi-IIb are responsib le for regulated epithelial Na-dependent P-i transport in all vertebrates. Most species express two different NaPi-II proteins with the exception of t he 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.