Munc13-1-mediated Vesicle Priming Contributes to Secretory Amyloid Precursor Protein Processing
The amyloid precursor protein (APP) gives rise toc β-amyloid peptides, which are the main constituents of senile plaques in brains of Alzheimer's disease patients. Non-amyloidogenic processing of the APP can be stimulated by phorbol esters (PEs) and by intracellular diacylglycerol (DAG) genera...
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Published in | The Journal of biological chemistry Vol. 279; no. 27; pp. 27841 - 27844 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Biochemistry and Molecular Biology
02.07.2004
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Subjects | |
Online Access | Get full text |
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Summary: | The amyloid precursor protein (APP) gives rise toc β-amyloid peptides, which are the main constituents of senile plaques in
brains of Alzheimer's disease patients. Non-amyloidogenic processing of the APP can be stimulated by phorbol esters (PEs)
and by intracellular diacylglycerol (DAG) generation. This led to the hypothesis that classical and novel protein kinase Cs
(PKCs), which are activated by DAG/PEs, regulate APP processing. However, in addition to PKCs, there are other DAG/PE receptors
present in neurons that may participate in the modulation of APP processing. Munc13-1, a presynaptic protein with an essential
role in synaptic vesicle priming, represents such an alternative target of the DAG second messenger pathway. Using Munc13-1
knock-out mice and knock-in mice expressing a Munc13-1(H567K) variant deficient in DAG/PE binding, we determined the relative
contributions of PKCs and Munc13-1 to PE-stimulated secretory APP processing. We establish that, in addition to PKC, Munc13-1
significantly contributes to the regulation of secretory APP metabolism. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.C400122200 |