Characterization of human presenilin 1 using N-terminal specific monoclonal antibodies: Evidence that Alzheimer mutations affect proteolytic processing
| Autor: | Miyuki Murayama, Kasutomo Imahori, Yuko Nakazato, Marc Mercken, Kazuki Sato, Toshiyuki Honda, Akihiko Takashima, Hiroshi Takahashi, Kaori Noguchi |
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| Rok vydání: | 1996 |
| Předmět: |
Biochemistry
PC12 Cells Epitope Epitopes Structural Biology Integral membrane protein Cells Cultured Glutathione Transferase chemistry.chemical_classification Antibodies Monoclonal Brain Transfection Chromosome 14 Amino acid Transmembrane domain Electrophoresis Polyacrylamide Gel Monoclonal antibody medicine.drug_class Recombinant Fusion Proteins Blotting Western Molecular Sequence Data Biophysics Biology Presenilin Alzheimer Disease mental disorders Genetics medicine Escherichia coli Presenilin-1 Animals Humans Amino Acid Sequence Molecular Biology Gene Membrane Proteins Cell Biology Molecular biology Peptide Fragments nervous system diseases Rats Molecular Weight chemistry nervous system Proteolysis Mutation Protein Processing Post-Translational |
| Zdroj: | FEBS letters. 389(3) |
| ISSN: | 0014-5793 |
| Popis: | The majority of cases of early-onset familial Alzheimer disease are caused by mutations in the recently identified presenilin 1 (PS1) gene, located on chromosome 14. PS1, a 467 amino acid protein, is predicted to be an integral membrane protein containing seven putative transmembrane domains and a large hydrophilic loop between the sixth and seventh membrane-spanning domain. We produced 7 monoclonal antibodies that react with 3 non-overlapping epitopes on the N-terminal hydrophilic tail of PS1. The monoclonal antibodies can detect the full-size PS1 at M r 47 000 and a more abundant M r 28 000 product in membrane extracts from human brain and human cell lines. PC12 cells transiently transfected with PS1 constructs containing two different Alzheimer mutations fail to generate the 28 kDa degradation product in contrast to PC12 cells transfected with wild-type PS1. Our results indicate that missense mutations in this form of familial Alzheimer disease may act via a mechanism of impaired proteolytic processing of PS1. |
| Databáze: | OpenAIRE |
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