A splice variant of beta-secretase deficient in the amyloidogenic processing of the amyloid precursor protein
| Autor: | Dale Lesley Bodian, Ursula Bodendorf, Frauke Fischer, Paolo Paganetti, Gerd Multhaup |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Amyloid
RNA Splicing Molecular Sequence Data Biochemistry Cell Line Amyloid beta-Protein Precursor Endopeptidases Amyloid precursor protein Animals Aspartic Acid Endopeptidases Humans Senile plaques Amino Acid Sequence RNA Messenger Molecular Biology Peptide sequence Secretory pathway biology Base Sequence Endoplasmic reticulum Alternative splicing Cell Biology DNA Immunohistochemistry Transmembrane protein biology.protein Amyloid Precursor Protein Secretases Amyloid precursor protein secretase |
| Zdroj: | The Journal of biological chemistry. 276(15) |
| ISSN: | 0021-9258 |
| Popis: | beta-Secretase (BACE) initiates the amyloidogenic processing of the amyloid precursor protein leading to the generation of the beta-amyloid, the main component of Alzheimer's disease senile plaques. BACE is a type I transmembrane aspartyl protease of 501 amino acids. Here we describe a novel BACE mRNA lacking 132 base pairs that is expressed in the pancreas but not in the brain. Sequence alignment indicates that the deleted fragment matches the terminal two-thirds of exon 3. The new BACE variant is short of a 44-amino acid region located between the two catalytic aspartyl residues. Accordingly, a 50-kDa form of BACE (BACE457) is detected in the human pancreas. When expressed in cells, BACE457 colocalizes with the marker for the endoplasmic reticulum BiP. Moreover, BACE457 remains in a proenzymatic and endoglycosidase H-sensitive state, suggesting that its transport along the secretory pathway is blocked at the level of the endoplasmic reticulum. Notably, this novel form of BACE does not contribute to the processing of the amyloid precursor protein. Our findings suggest that tissue-specific splicing of the BACE mRNA may explain the observation that in the human pancreas robust transcription of the BACE gene does not translate into recovered enzymatic activity. |
| Databáze: | OpenAIRE |
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