Amyloid-beta protein precursor (AbetaPP) intracellular domain-associated protein-1 proteins bind to AbetaPP and modulate its processing in an isoform-specific manner
| Autor: | Luciano D'Adamio, Cristiana Noviello, Enrico Ghersi |
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| Rok vydání: | 2004 |
| Předmět: |
Gene isoform
Cytoplasm DNA Complementary Time Factors Transcription Genetic Recombinant Fusion Proteins Amino Acid Motifs Blotting Western Molecular Sequence Data Enzyme-Linked Immunosorbent Assay Plasma protein binding Biology Transfection Biochemistry Cell Line Amyloid beta-Protein Precursor Mice Protein structure Extracellular Transcriptional regulation Fluorescence Resonance Energy Transfer Animals Humans Protein Isoforms Tissue Distribution Cloning Molecular Protein precursor Luciferases Molecular Biology Glutathione Transferase Neurons Alternative splicing Intracellular Signaling Peptides and Proteins Brain Cell Biology Exons Transmembrane protein Protein Structure Tertiary Mutation Carrier Proteins Peptides Gene Deletion HeLa Cells Protein Binding |
| Zdroj: | The Journal of biological chemistry. 279(47) |
| ISSN: | 0021-9258 |
| Popis: | The amyloid-beta protein precursor (AbetaPP) is a type I transmembrane molecule that undergoes several finely regulated cleavage events. The physiopathological relevance of AbetaPP derives from the fact that its aberrant processing strongly correlates with the onset of Alzheimer's disease (AD). AD is a neurodegenerative disorder characterized by neuronal cell death, loss of synapses, and deposition of misfolded protein plaques in the brain; the main constituent of these plaques is the amyloid-beta peptide, a 40-42 amino-acid-long protein fragment derived by AbetaPP upon two sequential processing events. Mutations in the genes encoding for AbetaPP and some of the enzymes responsible for its processing are strongly associated with familial forms of early onset AD. Therefore, the elucidation of the mechanisms underlying AbetaPP metabolism appears crucial to understanding the basis for the onset of AD. Apart from Abeta, upon processing of AbetaPP other fragments are generated. The long extracellular domain is released in the extracellular space, whereas the short cytoplasmic tail, named AbetaPP intracellular domain (AID) is released intracellularly. AID appears be involved in several cellular processes, apoptosis, calcium homeostasis, and transcriptional regulation. We have recently reported the cloning and characterization of different isoforms of AID associated protein-1 (AIDA-1), a novel AID-binding protein. Here we further analyzed the interaction between several AIDA-1 isoforms and the cytoplasmic tail of AbetaPP. Our data demonstrated that the interaction between the two molecules is regulated by alternative splicing of the AIDA-1 proteins. Furthermore, we provide data supporting a possible function for AIDA-1a as a modulator of AbetaPP processing. |
| Databáze: | OpenAIRE |
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