Amyloid-β Protein Precursor (AβPP) intracellular domain-associated protein-1 proteins bind to AβPP and modulate its processing in an isoform-specific manner

Enrico Ghersi, Cristiana Noviello, Luciano D'Adamio

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Abstract

The amyloid-β protein precursor (AβPP) is a type I transmembrane molecule that undergoes several finely regulated cleavage events. The physiopathological relevance of AβPP 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-β peptide, a 40-42 amino-acid-long protein fragment derived by AβPP upon two sequential processing events. Mutations in the genes encoding for AβPP 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 AβPP metabolism appears crucial to understanding the basis for the onset of AD. Apart from Aβ, upon processing of AβPP other fragments are generated. The long extracellular domain is released in the extracellular space, whereas the short cytoplasmic tail, named AβPP 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 AβPP. 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 AβPP processing.

Original languageEnglish (US)
Pages (from-to)49105-49112
Number of pages8
JournalJournal of Biological Chemistry
Volume279
Issue number47
DOIs
StatePublished - Nov 19 2004

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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