High resolution imaging study of interactions between the 37 kDa/67 kDa laminin receptor and APP, beta-secretase and gamma-secretase in Alzheimer's disease.

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dc.citation.doi10.1371/journal.pone.0100373.en_ZA
dc.citation.issue6en_ZA
dc.contributor.authorJovanovic, K.
dc.contributor.authorLoos, B.
dc.contributor.authorDa Costa Dias, B.
dc.contributor.authorPenny, C.
dc.contributor.authorWeiss, S.F.T.
dc.date.accessioned2016-10-17T10:27:07Z
dc.date.available2016-10-17T10:27:07Z
dc.date.issued2014-06-27
dc.description.abstractAlzheimer's disease (AD) is the most prevalent form of dementia affecting the elderly. Neurodegeneration is caused by the amyloid beta (Aβ) peptide which is generated from the sequential proteolytic cleavage of the Amyloid Precursor Protein (APP) by the β- and γ- secretases. Previous reports revealed that the 37 kDa/67 kDa laminin receptor (LRP/LR) is involved in APP processing, however, the exact mechanism by which this occurs remains largely unclear. This study sought to assess whether LRP/LR interacted with APP, β- or γ-secretase. Detailed confocal microscopy revealed that LRP/LR showed a strong co-localisation with APP, β- and γ-secretase, respectively, at various sub-cellular locations. Superresolution Structured Illumination Microscopy (SR-SIM) showed that interactions were unlikely between LRP/LR and APP and β-secretase, respectively, while there was strong co-localisation between LRP/LR and γ-secretase at this 80 nm resolution. FRET was further employed to assess the possibility of protein-protein interactions and only an interaction between LRP/LR and γ-secretase was found. FLAG co-immunoprecipitation confirmed these findings as LRP/LR co-immunoprecipitated with γ-secretase, but failed to do so with APP. These findings indicate that LRP/LR exerts its influence on Aβ shedding via a direct interaction with the γ-secretase and possibly an indirect interaction with the β-secretase.en_ZA
dc.description.librarianNCS2016.en_ZA
dc.description.sponsorshipThis work is based upon research supported by the National Research Foundation (NRF), the Republic of South Africa (RSA).en_ZA
dc.identifier.citationJovanovic, K.et al.2014 . High resolution imaging study of interactions between the 37 kDa/67 kDa laminin receptor and APP, beta-secretase and gamma-secretase in Alzheimer's disease. PLoS ONE 9(6):e100373.en_ZA
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/10539/21213
dc.journal.titlePLoS ONE.en_ZA
dc.journal.volume9en_ZA
dc.language.isoenen_ZA
dc.publisherPublic Library of Science.en_ZA
dc.rights© 2014 Jovanovic et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.subjectamyloid precursor proteinen_ZA
dc.subjectbeta secretaseen_ZA
dc.subjectgamma secretaseen_ZA
dc.subjectlaminin receptoren_ZA
dc.subjectamyloid precursor proteinen_ZA
dc.subjectlaminin receptoren_ZA
dc.subjectprotein bindingen_ZA
dc.subjectsecretaseen_ZA
dc.subjectAlzheimer diseaseen_ZA
dc.subjectcellular distributionen_ZA
dc.subjectconfocal microscopyen_ZA
dc.subjectcontrolled studyen_ZA
dc.subjectfluorescence resonance energy transferen_ZA
dc.subjecthuman cellen_ZA
dc.subjectimmunoprecipitationen_ZA
dc.subjectmicroscopyen_ZA
dc.subjectprotein interactionen_ZA
dc.subjectsuperresolution structured illumination microscopyen_ZA
dc.subjectcell lineen_ZA
dc.subjectchemistryen_ZA
dc.subjectmetabolismen_ZA
dc.subjectmolecular imagingen_ZA
dc.subjectproceduresen_ZA
dc.subjectprotein transporten_ZA
dc.subjectreporter geneen_ZA
dc.titleHigh resolution imaging study of interactions between the 37 kDa/67 kDa laminin receptor and APP, beta-secretase and gamma-secretase in Alzheimer's disease.en_ZA
dc.typeArticleen_ZA
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