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.

Show simple item record

dc.contributor.author Jovanovic, K.
dc.contributor.author Loos, B.
dc.contributor.author Da Costa Dias, B.
dc.contributor.author Penny, C.
dc.contributor.author Weiss, S.F.T.
dc.date.accessioned 2016-10-17T10:27:07Z
dc.date.available 2016-10-17T10:27:07Z
dc.date.issued 2014-06-27
dc.identifier.citation Jovanovic, 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.issn 1932-6203
dc.identifier.uri http://hdl.handle.net/10539/21213
dc.description.abstract Alzheimer'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.sponsorship This work is based upon research supported by the National Research Foundation (NRF), the Republic of South Africa (RSA). en_ZA
dc.language.iso en en_ZA
dc.publisher Public 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.subject amyloid precursor protein en_ZA
dc.subject beta secretase en_ZA
dc.subject gamma secretase en_ZA
dc.subject laminin receptor en_ZA
dc.subject amyloid precursor protein en_ZA
dc.subject laminin receptor en_ZA
dc.subject protein binding en_ZA
dc.subject secretase en_ZA
dc.subject Alzheimer disease en_ZA
dc.subject cellular distribution en_ZA
dc.subject confocal microscopy en_ZA
dc.subject controlled study en_ZA
dc.subject fluorescence resonance energy transfer en_ZA
dc.subject human cell en_ZA
dc.subject immunoprecipitation en_ZA
dc.subject microscopy en_ZA
dc.subject protein interaction en_ZA
dc.subject superresolution structured illumination microscopy en_ZA
dc.subject cell line en_ZA
dc.subject chemistry en_ZA
dc.subject metabolism en_ZA
dc.subject molecular imaging en_ZA
dc.subject procedures en_ZA
dc.subject protein transport en_ZA
dc.subject reporter gene en_ZA
dc.title 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. en_ZA
dc.type Article en_ZA
dc.journal.volume 9 en_ZA
dc.journal.title PLoS ONE. en_ZA
dc.description.librarian NCS2016. en_ZA
dc.citation.doi 10.1371/journal.pone.0100373. en_ZA
dc.citation.issue 6 en_ZA


Files in this item

This item appears in the following Collection(s)

Show simple item record

Search WIReDSpace


Browse

My Account