Regulation of ion channels by secreted Klotho

Klotho is an anti-aging protein predominantly expressed in the kidney, parathyroid glands and choroid plexus of the brain. Klotho exists in two forms, a membrane form and a soluble secreted form. Recent studies show that the secreted Klotho possess sialidase activity and regulates several ion channels via the activity. Removal of terminal sialic acids from N-glycan chains of the epithelial Ca ²⁺ channel TRPV5 and the renal K ⁺ channel ROMK by secreted Klotho exposes the underlying disaccharide galactose-N- acetylglucosamine, a ligand for galectin-1. Binding to galectin-1 at the extracellular surface prevents internalization and leads to accumulation of the channels on the plasma membrane. Future studies will investigate whether secreted Klotho regulates cell-surface expression of other membrane glycoproteins via the same mechanism.