The intracellular localization of amyloid β protein precursor (AβPP) intracellular domain associated protein-1 (AIDA-1) is regulated by AβPP and alternative splicing
| Autor: | Mona Abdallah, Peter Lopez, Pasquale Vito, Luciano D'Adamio, Enrico Ghersi |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Intracellular Fluid
Gene isoform DNA Complementary Molecular Sequence Data Biology Cell membrane Amyloid beta-Protein Precursor Fetus Alzheimer Disease Cell Line Tumor Precursor B-Cell Lymphoblastic Leukemia-Lymphoma medicine Humans Cloning Molecular Protein precursor Cells Cultured Neurons General Neuroscience Alternative splicing Intracellular Signaling Peptides and Proteins Brain General Medicine Transfection Peptide Fragments Transmembrane protein Alternative Splicing Psychiatry and Mental health Clinical Psychology medicine.anatomical_structure Gene Expression Regulation Biochemistry NUMB Geriatrics and Gerontology Carrier Proteins Intracellular |
| Zdroj: | Journal of Alzheimer's Disease. 6:67-78 |
| ISSN: | 1875-8908 1387-2877 |
| DOI: | 10.3233/jad-2004-6108 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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