Molecular dissection of the interaction between amyloid precursor protein and its neuronal trafficking receptor SorLA/LR11 - Analytical Methods & Tools for Lyophilization

Molecular dissection of the interaction between amyloid precursor protein and its neuronal trafficking receptor SorLA/LR11
Engineering Village 2
2006 Elsevier Inc.
Accession number: 06099737293

Title: Molecular dissection of the interaction between amyloid precursor protein and its neuronal trafficking receptor SorLA/LR11

Authors: Andersen, Olav M.; Schmidt, Vanessa; Spoelgen, Robert; Gliemann, Jorgen; Behlke, Joachim; Galatis, Denise; McKinstry, William J.; Parker, Michael W.; Masters, Colin L.; Hyman, Bradley T.; Cappai, Roberta; Willnow, Thomas E.

Author affiliation: Max-Delbrueck-Center for Molecular Medicine, Berlin, 13125 Berlin, Germany

Serial title: Biochemistry

Abbreviated serial title: Biochemistry

Volume: v 45

Issue: n 8

Issue date: Feb 28 2006

Publication year: 2006

Pages: p 2618-2628

Language: English

ISSN: 0006-2960

CODEN: BICHAW

Document type: Journal article (JA)

Publisher: American Chemical Society, Columbus, OH 43210-3337, United States

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-? peptide (A?), 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. ? 2006 American Chemical Society.

Number of references: 52

Ei main heading: Proteins

Ei controlled terms: Neurology - Molecular orientation - Fluorescence - Bioassay - Resonance - Patient monitoring

Uncontrolled terms: Surface plasmon resonance analysis - Carbohydrate-linked domains - Senile plaque formation - Neuronal trafficking receptors

Ei classification codes: 804.1 Organic Compounds - 461.6 Medicine - 931.1 Mechanics - 741.1 Light/Optics - 801 Chemistry - 701 Electricity and Magnetism - 462.2 Hospitals, Equipment & Supplies

Treatment: Literature review (LIT); Theoretical (THR); Experimental (EXP)

DOI: 10.1021/bi052120v

Database: Compendex

Compilation and indexing terms, ? 2006 Elsevier Inc. All rights reserved
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