RGD Reference Report - Amyloid precursor protein interacts with notch receptors. - Rat Genome Database

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Amyloid precursor protein interacts with notch receptors.

Authors: Oh, SY  Ellenstein, A  Chen, CD  Hinman, JD  Berg, EA  Costello, CE  Yamin, R  Neve, RL  Abraham, CR 
Citation: Oh SY, etal., J Neurosci Res. 2005 Oct 1;82(1):32-42.
RGD ID: 1581404
Pubmed: PMID:16118793   (View Abstract at PubMed)
DOI: DOI:10.1002/jnr.20625   (Journal Full-text)

The amyloid precursor protein (APP) must fulfill important roles based on its sequence conservation from fly to human. Although multiple functions for APP have been proposed, the best-known role for this protein is as the precursor of Abeta peptide, a neurotoxic 39-43-amino acid peptide crucial to the pathogenesis of Alzheimer's disease. To investigate additional roles for APP with an eye toward understanding the molecular basis of the pleiotropic effects ascribed to APP, we isolated proteins that interacted with the plasma membrane isoform of APP. We employed a membrane-impermeable crosslinker to immobilize proteins binding to transmembrane APP in human embryonic kidney (HEK)293 cells expressing APP751 (HEK275) or rat embryonic day 18 primary neurons infected with a virus expressing APP. Notch2 was identified as a potential APP binding partner based on mass spectrometry analysis of APP complexes immunopurified from neurons. To confirm the interaction between Notch2 and APP, we carried out immunoprecipitation studies in HEK275 cells transiently expressing full-length Notch2 using Notch2 antibodies. The results indicated that APP and Notch2 interact in mammalian cells, and confirmed our initial findings. Interestingly, Notch1 also coimmunoprecipitated with APP, suggesting that APP and Notch family members may engage in intermolecular cross talk to modulate cell function. Finally, cotransfection of APP/CFP and Notch2/YFP into COS cells revealed that these two proteins colocalize on the plasma membrane. Intracellularly, however, although some APP and Notch molecules colocalize, others reside in distinct locations. The discovery of proteins that interact with APP may aid in the identification of new functions for APP.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Notch2Rattissue regeneration  IEP  RGD 
Notch3Rattissue regeneration  IEP  RGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
AppRatprotein binding  IPINotch2 (Rattus norvegicus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
App  (amyloid beta precursor protein)
Notch2  (notch receptor 2)
Notch3  (notch receptor 3)


Additional Information