The intracellular localization of amyloid beta protein precursor (AbetaPP) intracellular domain associated protein-1 (AIDA-1) is regulated by AbetaPP and alternative splicing.
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.
Ghersi
Enrico
E
Albert Einstein College of Medicine, Department of Microbiology and Immunology, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Vito
Pasquale
P
Lopez
Peter
P
Abdallah
Mona
M
D'Adamio
Luciano
L
D017398:Alternative Splicing / Q000235:genetics; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D001921:Brain / Q000196:embryology / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D005333:Fetus; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D009474:Neurons / Q000473:pathology; D010446:Peptide Fragments / Q000235:genetics*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
C489945:ANKS1B protein, human; D016564:Amyloid beta-Protein Precursor; D002352:Carrier Proteins; D018076:DNA, Complementary; D047908:Intracellular Signaling Peptides and Proteins; D010446:Peptide Fragments