Amyloid-beta protein precursor (AbetaPP) intracellular domain-associated protein-1 proteins bind to AbetaPP and modulate its processing in an isoform-specific manner.
The amyloid-beta protein precursor (AbetaPP) is a type I transmembrane molecule that undergoes several finely regulated cleavage events. The physiopathological relevance of AbetaPP derives from the fact that its aberrant processing strongly correlates with the onset of Alzheimer's disease (AD). AD is a neurodegenerative disorder characterized by neuronal cell death, loss of synapses, and deposition of misfolded protein plaques in the brain; the main constituent of these plaques is the amyloid-beta peptide, a 40-42 amino-acid-long protein fragment derived by AbetaPP upon two sequential processing events. Mutations in the genes encoding for AbetaPP and some of the enzymes responsible for its processing are strongly associated with familial forms of early onset AD. Therefore, the elucidation of the mechanisms underlying AbetaPP metabolism appears crucial to understanding the basis for the onset of AD. Apart from Abeta, upon processing of AbetaPP other fragments are generated. The long extracellular domain is released in the extracellular space, whereas the short cytoplasmic tail, named AbetaPP intracellular domain (AID) is released intracellularly. AID appears be involved in several cellular processes, apoptosis, calcium homeostasis, and transcriptional regulation. We have recently reported the cloning and characterization of different isoforms of AID associated protein-1 (AIDA-1), a novel AID-binding protein. Here we further analyzed the interaction between several AIDA-1 isoforms and the cytoplasmic tail of AbetaPP. Our data demonstrated that the interaction between the two molecules is regulated by alternative splicing of the AIDA-1 proteins. Furthermore, we provide data supporting a possible function for AIDA-1a as a modulator of AbetaPP processing.
Ghersi
Enrico
E
Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA.
Noviello
Cristiana
C
D'Adamio
Luciano
L
D020816:Amino Acid Motifs; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry* / Q000235:genetics*; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics; D002460:Cell Line; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005091:Exons; D031541:Fluorescence Resonance Energy Transfer; D017353:Gene Deletion; D005982:Glutathione Transferase / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D010455:Peptides; D011485:Protein Binding; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D013997:Time Factors; D014018:Tissue Distribution; D014158:Transcription, Genetic; D014162:Transfection
C489945:ANKS1B protein, human; D016564:Amyloid beta-Protein Precursor; D002352:Carrier Proteins; D018076:DNA, Complementary; D047908:Intracellular Signaling Peptides and Proteins; D010455:Peptides; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D008156:Luciferases; D005982:Glutathione Transferase