Fe65 and the protein network centered around the cytosolic domain of the Alzheimer's beta-amyloid precursor protein. 1998

T Russo, and R Faraonio, and G Minopoli, and P De Candia, and S De Renzis, and N Zambrano
Dipartimento di Biochimica e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Naples, Italy. russoto@unina.it

A distinctive tract of all the forms of Alzheimer's disease is the extracellular deposition of a 40-42/43 amino acid-long peptide derived from the so-called beta-amyloid precursor protein (APP). This is a membrane protein of unknown function, whose short cytosolic domain has been recently demonstrated to interact with several proteins. One of these proteins, named Fe65, has the characteristics of an adaptor protein; in fact, it possesses three protein-protein interaction domains: a WW domain and two PID/PTB domains. The interaction with APP requires the most C-terminal PID/PTB domain, whereas the WW domain is responsible for the interaction with various proteins, one of which was demonstrated to be the mammalian homolog of the Drosophila enabled protein (Mena), which in turn interacts with the cytoskeleton. The second PID/PTB domain of Fe65 binds to the CP2/LSF/LBP1 protein, which is an already known transcription factor. The other proteins interacting with the cytosolic domain of APP are the G(o) heterotrimeric protein, APP-BP1 and X11. The latter interacts with APP through a PID/PTB domain and possesses two other protein-protein interaction domains. The small size of the APP cytodomain and the overlapping of its regions involved in the binding of Fe65 and X11 suggest the existence of competitive mechanisms regulating the binding of the various ligands to this cytosolic domain. In this short review the possible functional roles of this complex protein network and its involvement in the generation of Alzheimer's phenotype are discussed.

UI MeSH Term Description Entries
D009419 Nerve Tissue Proteins Proteins, Nerve Tissue,Tissue Proteins, Nerve
D009687 Nuclear Proteins Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus. Nucleolar Protein,Nucleolar Proteins,Nuclear Protein,Protein, Nuclear,Protein, Nucleolar,Proteins, Nuclear,Proteins, Nucleolar
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D003600 Cytosol Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components. Cytosols
D004330 Drosophila A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology. Fruit Fly, Drosophila,Drosophila Fruit Flies,Drosophila Fruit Fly,Drosophilas,Flies, Drosophila Fruit,Fly, Drosophila Fruit,Fruit Flies, Drosophila
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000544 Alzheimer Disease A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57) Acute Confusional Senile Dementia,Alzheimer's Diseases,Dementia, Alzheimer Type,Dementia, Senile,Presenile Alzheimer Dementia,Senile Dementia, Alzheimer Type,Alzheimer Dementia,Alzheimer Disease, Early Onset,Alzheimer Disease, Late Onset,Alzheimer Sclerosis,Alzheimer Syndrome,Alzheimer Type Senile Dementia,Alzheimer's Disease,Alzheimer's Disease, Focal Onset,Alzheimer-Type Dementia (ATD),Dementia, Presenile,Dementia, Primary Senile Degenerative,Early Onset Alzheimer Disease,Familial Alzheimer Disease (FAD),Focal Onset Alzheimer's Disease,Late Onset Alzheimer Disease,Primary Senile Degenerative Dementia,Senile Dementia, Acute Confusional,Alzheimer Dementias,Alzheimer Disease, Familial (FAD),Alzheimer Diseases,Alzheimer Type Dementia,Alzheimer Type Dementia (ATD),Alzheimers Diseases,Dementia, Alzheimer,Dementia, Alzheimer-Type (ATD),Familial Alzheimer Diseases (FAD),Presenile Dementia,Sclerosis, Alzheimer,Senile Dementia
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D016564 Amyloid beta-Protein Precursor A single-pass type I membrane protein. It is cleaved by AMYLOID PRECURSOR PROTEIN SECRETASES to produce peptides of varying amino acid lengths. A 39-42 amino acid peptide, AMYLOID BETA-PEPTIDES is a principal component of the extracellular amyloid in SENILE PLAQUES. Amyloid A4 Protein Precursor,Amyloid Protein Precursor,beta-Amyloid Protein Precursor,Amyloid beta Precursor Protein,Protease Nexin 2,Protease Nexin II,Amyloid beta Protein Precursor,Nexin 2, Protease,Nexin II, Protease,beta Amyloid Protein Precursor,beta-Protein Precursor, Amyloid

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