Soluble Alpha-APP (sAPPalpha) Regulates CDK5 Expression and Activity in Neurons |
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| Authors: | Daniela Hartl Stephan Klatt Manfred Roch Zoltan Konthur Joachim Klose Thomas E Willnow Michael Rohe |
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| Institution: | 1. Institute for Medical Genetics and Human Genetics, Charité - University Medicine, Berlin, Germany.; 2. Max Planck Institute for Molecular Genetics, Berlin, Germany.; 3. Free University Berlin, Faculty of Biology, Chemistry and Pharmacy; Berlin, Germany.; 4. Max Planck Institute of Colloids and Interfaces, Potsdam, Germany.; 5. Max-Delbrueck-Center for Molecular Medicine, Berlin, Germany.; Oregon Health and Science University, United States of America, |
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| Abstract: | A growing body of evidence suggests a role for soluble alpha-amyloid precursor protein (sAPPalpha) in pathomechanisms of Alzheimer disease (AD). This cleavage product of APP was identified to have neurotrophic properties. However, it remained enigmatic what proteins, targeted by sAPPalpha, might be involved in such neuroprotective actions. Here, we used high-resolution two-dimensional polyacrylamide gel electrophoresis to analyze proteome changes downstream of sAPPalpha in neurons. We present evidence that sAPPalpha regulates expression and activity of CDK5, a kinase that plays an important role in AD pathology. We also identified the cytoprotective chaperone ORP150 to be induced by sAPPalpha as part of this protective response. Finally, we present functional evidence that the sAPPalpha receptor SORLA is essential to mediate such molecular functions of sAPPalpha in neurons. |
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