Klotho is a substrate for α-, β- and γ-secretase

Laura Bloch, Olga Sineshchekova, Daniela Reichenbach, Karina Reiss, Paul Saftig, Makoto Kuro-o, Christoph Kaether

Research output: Contribution to journalArticlepeer-review

206 Scopus citations


Klotho is an anti-aging protein with different functions of the full-length membrane protein and the secreted hormone-like form. Using overexpression and knock-down approaches as well as embryonic fibroblasts of knock-out mice we present evidence that Klotho is shedded by the α-secretases ADAM10 and 17 as well as by the β-secretase β-APP cleaving enzyme 1. The remaining membrane-bound fragment is a substrate for regulated intramembrane proteolysis by γ-secretase. Our data suggest that therapeutic approaches targeting these proteases should be carefully analyzed for potential side effects on Klotho-mediated physiological processes.

Original languageEnglish (US)
Pages (from-to)3221-3224
Number of pages4
JournalFEBS Letters
Issue number19
StatePublished - Oct 6 2009


  • ADAM protease
  • Klotho
  • β-APP cleaving enzyme
  • γ-Secretase

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology


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