Regulation of ion channels by secreted Klotho: mechanisms and implications.
Klotho is an anti-aging protein predominantly expressed in the kidney, parathyroid glands, and choroid plexus of the brain. It is a single-pass transmembrane protein with a large extracellular domain. The extracellular domain of Klotho is cleaved and released into extracellular fluid, including blood, urine, and cerebrospinal fluid. The membrane-bound full-length Klotho and secreted extracellular domain of Klotho have distinct functions. Membrane Klotho interacts with fibroblast growth factor (FGF) receptors to form high-affinity receptors for FGF23. Secreted Klotho functions as a humoral factor that regulates several ion channels and transporters, and other processes, including insulin and insulin-like growth factor signaling. This mini-review focuses on the mechanisms of regulation of cell-surface abundance of ion channels by secreted Klotho and the importance of these effects of Klotho in physiology and pathological conditions.
Huang
Chou-Long
CL
Department of Medicine, UT Southwestern Medical Center, Dallas, Texas, USA.chou-long.huang@utsouthwestern.edu
D000375:Aging / Q000502:physiology*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D000089703:Fibroblast Growth Factor-23; D007328:Insulin / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism; D007477:Ions / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D051379:Mice; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
C000717428:Fgf23 protein, mouse; D007328:Insulin; D007473:Ion Channels; D007477:Ions; D017468:Receptors, Fibroblast Growth Factor; D000089703:Fibroblast Growth Factor-23