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J Alzheimers Dis. 2004 Feb;6(1):67-78.

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

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  • 1Albert Einstein College of Medicine, Department of Microbiology and Immunology, 1300 Morris Park Avenue, Bronx, NY 10461, USA.

Abstract

The Amyloid-beta Protein Precursor (AbetaPP) 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, AbetaPP releases the Amyloid-beta (Abeta) peptide, which accumulates in insoluble plaques in the brain of patients affected by Alzheimer's Disease (AD). Another peptide, a C-terminal fragment named AbetaPP Intracellular Domain (AID), is generated by AbetaPP 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 X11alpha, 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-1bDeltaAnk. We show that AbetaPP and the AIDA-1 proteins interact in vitro, in living cells and, endogenously, in leukemia cell lines. Transfected AIDA-1a, AIDA-1b and AIDA-1bDeltaAnk localize in different compartments and the intracellular distribution of AIDA-1a can be modified by over-expression of AbetaPP. AIDA-1 proteins are expressed at high levels in the brain; thus, studying their involvement in AbetaPP 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.

PMID:
15004329
[PubMed - indexed for MEDLINE]
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