Notch 1 interacts with the amyloid precursor protein in a Numb-independent manner

✍ Scribed by Angeliki Fassa; Pankaj Mehta; Spiros Efthimiopoulos

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 742 KB
• Volume: 82
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.20642

✦ Synopsis

We hypothesized that the physical interaction between the amyloid precursor protein (APP) and Notch 1 (N1) may be mediating the reported cross-talk between the respective signaling pathways. Immunoprecipitation of mouse N1 (mN1) or extracellular domain truncated mN1 (mN1-TM, mimics TACE-produced membrane-bound C-terminal fragment) specifically coprecipitated APP 751 . Conversely, immunoprecipitation of APP 751 specifically coprecipitated mN1, furin-generated membrane-bound mN1 C-terminal fragment (f.mN1-TM), or mN1-TM. The London mutation of APP did not affect the APP 751 /mN1 interaction. Coexpression of APP 751 and mN1 did not affect APP processing or production of mN1 intracellular domain (mNICD). The APP 751 /mN1 interaction was Numb-independent, insofar as it was observed in HEK293 cells that lack detectable levels of Numb and was unaffected by the expression of exogenous Numb or deletion of the APP cytoplasmic domain, including the Numbbinding YENPTY sequence. This interaction was unaffected even when the N-terminal 647 amino acids of APP were replaced by a sequence of secreted alkaline phosphatase. These data combined with data showing interaction between mN1-TM and APP 751 suggest that their transmebrane domains and short sequences around them are sufficient for the interaction and that APP 751 and mN1 interact in cis. Our results imply novel functions of APP and/or N1 that derive from their interaction.