Novel adaptors of amyloid precursor protein intracellular domain and their functional implications.
Amyloid precursor protein intracellular domain (AICD) is one of the potential candidates in deciphering the complexity of Alzheimer's disease. It plays important roles in determining cell fate and neurodegeneration through its interactions with several adaptors. The presence or absence of phosphorylation at specific sites determines the choice of partners. In this study, we identified 20 novel AICD-interacting proteins by in vitro pull down experiments followed by 2D gel electrophoresis and MALDI-MS analysis. The identified proteins can be grouped into different functional classes including molecular chaperones, structural proteins, signaling and transport molecules, adaptors, motor proteins and apoptosis determinants. Interactions of nine proteins were further validated either by colocalization using confocal imaging or by co-immunoprecipitation followed by immunoblotting. The cellular functions of most of the proteins can be correlated with AD. Hence, illustration of their interactions with AICD may shed some light on the disease pathophysiology.
Structural Genomics Division, Saha Institute of Nuclear Physics, Kolkata, West Bengal, India.
Arunabha
A
Chakrabarti
Debashis
D
Mukhopadhyay
D000544:Alzheimer Disease / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry* / Q000378:metabolism*; D017209:Apoptosis; D002454:Cell Differentiation; D015180:Electrophoresis, Gel, Two-Dimensional; D050883:HSC70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D010766:Phosphorylation; D054730:Protein Interaction Domains and Motifs; D011506:Proteins / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014746:Vimentin / Q000378:metabolism
C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D050883:HSC70 Heat-Shock Proteins; C494371:HSPA8 protein, human; D011506:Proteins; D014746:Vimentin