Title:Regulation of Cellular Transport by Klotho Protein
Volume: 15
Issue: 8
Author(s): Mentor Sopjani, Mark Rinnerthaler, Ahmad Almilaji, Salih Ahmeti and Miribane Dermaku-Sopjani
Affiliation:
Keywords:
Klotho, aging supressor, cellular transport, carrier, Ion channel, pump.
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.
