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Klotho is a substrate for α‐, β‐ and γ‐secretase
Author(s) -
Bloch Laura,
Sineshchekova Olga,
Reichenbach Daniela,
Reiss Karina,
Saftig Paul,
Kuro-o Makoto,
Kaether Christoph
Publication year - 2009
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2009.09.009
Subject(s) - klotho , proteolysis , amyloid precursor protein secretase , proteases , adam10 , amyloid precursor protein , microbiology and biotechnology , chemistry , alpha secretase , biochemistry , enzyme , biology , medicine , endocrinology , metalloproteinase , kidney , alzheimer's disease , disintegrin , disease
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.