Na+-dependent phosphate cotransporters: The NaPi protein families

In vertebrates, the level of inorganic phosphate (P-i) is tightly balanced both inside the cell and in the whole organism, A number of different Na+-d ependent P-i cotransport systems involved in P-i homeostasis have been iden tified and characterized at the molecular level in the past 7 years. The tr ansporters constitute three different protein families denoted NaPi-I, NaPi -II and NaPi-III, NaPi-I from the rabbit was the first member of this famil y to be cloned. However, it still resists efforts to unravel its physiologi cal role and a clear-cut functional identity: is it a CI- channel, a Na+/P- i cotransporter, a regulator, or does it perform a combination of these fun ctions? These questions provide a slight taste of the problems associated w ith orphan genes derived from sequencing projects. The members of the NaPi- II: protein family are crucially involved in tightly controlled renal P-i e xcretion and, as recently discovered, intestinal P-i absorption. The expres sion and the cellular distribution of NaPi-II in the proximal tubular epith elium are affected by hormonal and metabolic factors known to influence ext racellular fluid P-i homeostasis. Recently, the expression of NaPi-II has b een demonstrated in osteoclasts and brain; however, the physiological roles of NaPi-II in these tissues remain to be established, The members of the t hird protein family, NaPi-III, have been identified on the basis of their f unction as viral receptors, The widespread expression of this family sugges ts that NaPi-III is involved in supplying the basic cellular metabolic need s for P-i.