Klotho is a Substrate for Alpha-, Beta- and Gamma-secretase

Overview

Journal FEBS Lett

Specialty Biochemistry

Date 2009 Sep 10

PMID 19737556

Citations 145

Authors

Laura Bloch

Olga Sineshchekova

Daniela Reichenbach

Karina Reiss

Paul Saftig

Makoto Kuro-O

Christoph Kaether

Affiliations

Soon will be listed here.

Abstract

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 alpha-secretases ADAM10 and 17 as well as by the beta-secretase beta-APP cleaving enzyme 1. The remaining membrane-bound fragment is a substrate for regulated intramembrane proteolysis by gamma-secretase. Our data suggest that therapeutic approaches targeting these proteases should be carefully analyzed for potential side effects on Klotho-mediated physiological processes.

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