The intracellular localization of amyloid β protein precursor (AβPP) intracellular domain associated protein-1 (AIDA-1) is regulated by AβPP and alternative splicing

Enrico Ghersi, Pasquale Vito, Peter Lopez, Mona Abdallah, Luciano D'Adamio

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

The Amyloid-β Protein Precursor (AβPP) is a widely expressed transmembrane protein that is extensively processed in intracellular vesicular compartments and on the cell membrane. As a result of two sequential proteolytic cleavages, AβPP releases the Amyloid-β (Aβ) peptide, which accumulates in insoluble plaques in the brain of patients affected by Alzheimer's Disease (AD). Another peptide, a C-terminal fragment named AβPP Intracellular Domain (AID), is generated by AβPP processing and is released intracellularly. Several functions for AID have been proposed: pro-apoptotic peptide, regulator of calcium homeostasis, molecule involved in transcriptional regulation. Many intracellular proteins, such as Fe65, Jip-1, Shc, Numb and X11α, interact with AID and modulate its function by different mechanisms. Here we report the cloning and initial characterization of two isoforms of a novel protein that we named AID Associated protein-1a (AIDA-1a), AIDA-1b and AIDA-1bΔAnk. We show that AβPP and the AIDA-1 proteins interact in vitro, in living cells and, endogenously, in leukemia cell lines. Transfected AIDA-1a, AIDA-1b and AIDA-1bΔAnk localize in different compartments and the intracellular distribution of AIDA-1a can be modified by over-expression of AβPP. ADA-1 proteins are expressed at high levels in the brain; thus, studying their involvement in AβPP processing and AID function might give new insights regarding a possible role for these molecules in normal brain development and in the pathogenesis of AD.

Original languageEnglish (US)
Pages (from-to)67-78
Number of pages12
JournalJournal of Alzheimer's Disease
Volume6
Issue number1
DOIs
StatePublished - Feb 2004

Keywords

  • AID
  • AIDA-1
  • Alzheimer's disease
  • AβPP
  • EB-1
  • Interaction

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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