TY - JOUR
T1 - The intracellular localization of amyloid β protein precursor (AβPP) intracellular domain associated protein-1 (AIDA-1) is regulated by AβPP and alternative splicing
AU - Ghersi, Enrico
AU - Vito, Pasquale
AU - Lopez, Peter
AU - Abdallah, Mona
AU - D'Adamio, Luciano
PY - 2004/2
Y1 - 2004/2
N2 - 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.
AB - 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.
KW - AID
KW - AIDA-1
KW - Alzheimer's disease
KW - AβPP
KW - EB-1
KW - Interaction
UR - http://www.scopus.com/inward/record.url?scp=1842427832&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=1842427832&partnerID=8YFLogxK
U2 - 10.3233/JAD-2004-6108
DO - 10.3233/JAD-2004-6108
M3 - Article
C2 - 15004329
AN - SCOPUS:1842427832
SN - 1387-2877
VL - 6
SP - 67
EP - 78
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - 1
ER -