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Molecular Dissection of the Interaction between Amyloid Precursor Protein and Its Neuronal Trafficking Receptor SorLA/LR11
- Source :
- Biochemistry. 45:2618-2628
- Publication Year :
- 2006
- Publisher :
- American Chemical Society (ACS), 2006.
-
Abstract
- SorLA/LR11 is a sorting receptor that regulates the intracellular transport and processing of the amyloid precursor protein (APP) in neurons. SorLA/LR11-mediated binding results in sequestration of APP in the Golgi and in protection from processing into the amyloid-beta peptide (Abeta), the principal component of senile plaques in Alzheimer's disease (AD). To gain insight into the molecular mechanisms governing sorLA and APP interaction, we have dissected the respective protein interacting domains. Using a fluorescence resonance energy transfer (FRET) based assay of protein proximity, we identified binding sites in the extracellular regions of both proteins. Fine mapping by surface plasmon resonance analysis and analytical ultracentrifugation of recombinant APP and sorLA fragments further narrowed down the binding domains to the cluster of complement-type repeats in sorLA that forms a 1:1 stoichiometric complex with the carbohydrate-linked domain of APP. These data shed new light on the molecular determinants of neuronal APP trafficking and processing and on possible targets for intervention with senile plaque formation in patients with AD.
- Subjects :
- Time Factors
SORL1
Plasma protein binding
Transfection
Models, Biological
Biochemistry
Amyloid beta-Protein Precursor
Protein structure
mental disorders
Amyloid precursor protein
Humans
Senile plaques
Cells, Cultured
LDL-Receptor Related Proteins
Neurons
Microscopy, Confocal
biology
Chemistry
Brain
Membrane Transport Proteins
Surface Plasmon Resonance
LRP1
Protein Structure, Tertiary
Cell biology
Transport protein
Protein Transport
Förster resonance energy transfer
Receptors, LDL
biology.protein
Protein Binding
Subjects
Details
- ISSN :
- 15204995 and 00062960
- Volume :
- 45
- Database :
- OpenAIRE
- Journal :
- Biochemistry
- Accession number :
- edsair.doi.dedup.....4af522ad48faf5f7083a85eb1e9a75de