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

Article type: Research Article

Authors: Ghersi, Enrico^a | Vito, Pasquale^c | Lopez, Peter^d | Abdallah, Mona^e | D'Adamio, Luciano^{a; b; *}

Affiliations: [a] Albert Einstein College of Medicine, Department of Microbiology and Immunology, 1300 Morris Park Avenue, Bronx, N.Y. 10461, USA | [b] CEINGE-Biotecnologie Avanzate, Universita' degli Studi Federico II, Naples, 80131, Italy | [c] Dipartimento di Scienze Biologiche edAmbientali, Universita' degli Studi del Sannio, Benevento, Italy | [d] Aaron Diamond AIDS Research Center, Rockefeller University, New York, NY 10016, USA | [e] Zymed Laboratories, 561 Eccles Ave, South San Francisco, CA 94080, USA

Correspondence: [*] Corresponding author: Luciano D'Adamio, Albert Einstein College of Medicine, Department Of Microbiology and Immunology, 1300 Morris Park Avenue, Bronx, N.Y. 10461 USA. E-mail: [email protected].

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. AIDA-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.

Keywords: Alzheimer's disease, interaction, AβPP, AID, AIDA-1, EB-1

DOI: 10.3233/JAD-2004-6108

Journal: Journal of Alzheimer's Disease, vol. 6, no. 1, pp. 67-78, 2004