title: Downregulation of NaPi-IIa and NaPi-IIb Na-coupled phosphate transporters by coexpression of Klotho.
abstract: Klotho, a transmembrane protein, protease and hormone has been shown to exert a profound effect on phosphate metabolism. Klotho overexpression lowers and Klotho deficiency increases the plasma phosphate concentration, effects in part attributed to an inhibitory effect of Klotho on the formation of 1,25-dihydroxycholecalciferol (1,25(OH) (2)D(3)), the active form of Vitamin D. Beyond that Klotho has been shown to decrease renal tubular phosphate transport more directly. The influence of Klotho on the plasma phosphate concentration contributes to the profound effect of Klotho on ageing and life span. The present study explored whether Klotho influences the major renal tubular (NaPi-IIa) and the major intestinal (NaPi-IIb) phosphate transporters. For functional analysis NaPi-IIa or NaPi-IIb were expressed in Xenopus oocytes both, without or with additional coexpression of Klotho and electrogenic phosphate transport was estimated from the phosphate-induced current (Ip). According to RT-PCR Klotho is expressed in the murine kidney and intestine. Coexpression of Klotho decreased Ip in both NaPi-IIa- and NaPi-IIb-expressing oocytes. Klotho decreased the maximal Ip without appreciably affecting the concentration required for halfmaximal Ip. Treatment of NaPi-IIa- or NaPi-IIb-expressing oocytes with Klotho protein similarly decreased Ip. In conclusion, Klotho down regulates both, renal (NaPi-IIa) and intestinal (NaPi-IIb) phosphate transporters.
authors.affiliation: Department of Physiology, University of Tübingen, Tübingen, Germany.
authors.forename: Miribane
authors.initials: M
authors.lastname: Dërmaku-Sopjani
authors.forename: Mentor
authors.initials: M
authors.lastname: Sopjani
authors.forename: Ambrish
authors.initials: A
authors.lastname: Saxena
authors.forename: Manzar
authors.initials: M
authors.lastname: Shojaiefard
authors.forename: Evgenii
authors.initials: E
authors.lastname: Bogatikov
authors.forename: Ioana
authors.initials: I
authors.lastname: Alesutan
authors.forename: Melanie
authors.initials: M
authors.lastname: Eichenmüller
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000818:Animals; D002112:Calcifediol / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D000090265:Klotho Proteins; D051379:Mice; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D010710:Phosphates / Q000378:metabolism / Q000494:pharmacology; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D050614:Sodium-Phosphate Cotransporter Proteins, Type IIb / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D014982:Xenopus laevis
chemical_list: D010710:Phosphates; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa; D050614:Sodium-Phosphate Cotransporter Proteins, Type IIb; D005966:Glucuronidase; D000090265:Klotho Proteins; D002112:Calcifediol