Jovanovic, K.Loos, B.Da Costa Dias, B.Penny, C.Weiss, S.F.T.2016-10-172016-10-172014-06-27Jovanovic, 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):e100373.1932-6203http://hdl.handle.net/10539/21213Alzheimer'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© 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.amyloid precursor proteinbeta secretasegamma secretaselaminin receptoramyloid precursor proteinlaminin receptorprotein bindingsecretaseAlzheimer diseasecellular distributionconfocal microscopycontrolled studyfluorescence resonance energy transferhuman cellimmunoprecipitationmicroscopyprotein interactionsuperresolution structured illumination microscopycell linechemistrymetabolismmolecular imagingproceduresprotein transportreporter geneArticle