title: Regulation of cellular transport by klotho protein.
abstract: The antiaging protein of Klotho is a transmembrane protein mainly expressed in the kidney, parathyroid glands and choroid plexus of the brain. The Klotho protein exists in two forms, a full-length membrane form and a soluble secreted form. The extracellular domain of Klotho can be enzymatically cleaved off and released into the systemic circulation where it acts as β-glucuronidase and a hormone. Soluble Klotho can be found in the blood, cerebrospinal fluid, and the urine of mammals. Klotho deficiency results in early appearance of multiple age-related disorders and premature death, whereas overexpression of Klotho exerts the opposite effect. Klotho may influence cellular transport processes across the cell membrane by inhibiting calcitriol (1,25(OH) (2)D(3)), formation or by directly affecting transporter proteins, including ion channels, carriers and pumps. Accordingly, Klotho protein is a powerful regulator of transport mechanisms across the cell membrane. Klotho regulates diverse calcium and potassium ion channels, as well as several carriers including the Na(+)-coupled excitatory amino acid transporters EAAT3 and EAAT4, the Na(+)-coupled phosphate cotransporters, NaPi-IIa and NaPi-IIb, and a Na(+)/K(+)-ATPase. All those cellular transport regulations contribute in the aging suppressor role of Klotho. Future studies will help to determine if the Klotho protein regulates cell-surface expression of other transport proteins and is affecting underlying mechanisms.
authors.forename: Mentor
authors.initials: M
authors.lastname: Sopjani
authors.forename: Mark
authors.initials: M
authors.lastname: Rinnerthaler
authors.forename: Ahmad
authors.initials: A
authors.lastname: Almilaji
authors.forename: Salih
authors.initials: S
authors.lastname: Ahmeti
authors.affiliation: Faculty of Medicine of the University of Prishtina, Str. Bulevardi i Deshmoreve, p.n.; 10 000, Prishtina, Kosova. msopjani@yahoo.com.
authors.forename: Miribane
authors.initials: M
authors.lastname: Dermaku-Sopjani
mesh_terms: D000818:Animals; D001692:Biological Transport; D002477:Cells / Q000378:metabolism*; D005966:Glucuronidase / Q000378:metabolism*; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D000090265:Klotho Proteins; D008954:Models, Biological; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: D007473:Ion Channels; D005966:Glucuronidase; D000090265:Klotho Proteins; D000254:Sodium-Potassium-Exchanging ATPase