The role of low-density receptor-related protein 1 (LRP1) as a competitive substrate of the amyloid precursor protein (APP) for BACE1

Einem, Bjoern von; Schwanzar, Daniel; Rehn, Florian; Beyer, A.; Weber, Petra; Wagner, Michael; Schneckenburger, Herbert; Arnim, Christine A. F. Von

doi:10.1016/j.expneurol.2010.05.017

Cited by 32 publications

(23 citation statements)

References 38 publications

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“…Channels 1-3 and 15-16 are noisier than channels 4-14 for donor-EGFP alone, so the fitting procedure was done for three different data sets: (i) A fitting routine of the donor signal alone was performed for channel 11, (ii) a global fitting for 11 channels (channel [4][5][6][7][8][9][10][11][12][13][14], and (iii) a global fitting for 16 channels (channel 1-16). For the donor-EGFP only model, the energy transfer rate was considered K D ET = 0 because of the lack of energy transfer in the absence of the acceptor.…”

Section: Resultsmentioning

confidence: 99%

“…8,23,24 Cells were cotransfected with the proteins tagged to EGFP or mRFP, respectively. For control experiments cells were transfected with EGFP or mRFP alone or with a tandemprotein consisting of EGFP and mRFP linked by a peptide of 7 amino acids.…”

Section: Fluorophoresmentioning

confidence: 99%

“…GGA1-pcDNA3.1-myc, EGFP, mRFP, EGFP-mRFP tandem, and BACE-mRFP have been described elsewhere. 6,8,24 Authenticity was confirmed by deoxyribose nucleic acid (DNA) sequencing. …”

Section: Generation Of Expression Constructs Of Gga1mentioning

confidence: 99%

“…3 In the field of Alzheimer's disease (AD), it has been widely used to establish protein-protein interaction and also protein conformation. [4][5][6][7][8] However, FRET measurements and analysis in living cells is very challenging due to suboptimal excitation and emission overlap of donor and acceptor, high autofluorescence, low quantum yield of living color tags, reduced signal intensity of proteins with low abundancy, and hence, poor signal-to-noise (S/N) ratio. A very complex situation arises when more than one compound has to be analyzed.…”

Section: Introductionmentioning

confidence: 99%

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Spectrally resolved fluorescence lifetime imaging microscopy: Förster resonant energy transfer global analysis with a one- and two-exponential donor model

et al. 2011

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In many fields of life science, visualization of spatial proximity, as an indicator of protein interactions in living cells, is of outstanding interest. A method to accomplish this is the measurement of Förster resonant energy transfer (FRET) by means of spectrally resolved fluorescence lifetime imaging microscopy. The fluorescence lifetime is calculated using a multiple-wavelength fitting routine. The donor profile is assumed first to have a monoexponential time-dependent behavior, and the acceptor decay profile is solved analytically. Later, the donor profile is assumed to have a two-exponential time-dependent behavior and the acceptor decay profile is derived analytically. We develop and apply a multispectral fluorescence lifetime imaging microscopy analysis system for FRET global analysis with time-resolved and spectrally resolved techniques, including information from donor and acceptor channels in contrast to using just a limited spectral data set from one detector only and a model accounting only for the donor signal. This analysis is used to demonstrate close vicinity of β-secretase (BACE) and GGA1, two proteins involved in Alzheimer's disease pathology. We attempt to verify if an improvement in calculating the donor lifetimes could be achieved when time-resolved and spectrally resolved techniques are simultaneously incorporated.

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Section: Resultsmentioning

confidence: 99%

Section: Fluorophoresmentioning

confidence: 99%

“…GGA1-pcDNA3.1-myc, EGFP, mRFP, EGFP-mRFP tandem, and BACE-mRFP have been described elsewhere. 6,8,24 Authenticity was confirmed by deoxyribose nucleic acid (DNA) sequencing. …”

Section: Generation Of Expression Constructs Of Gga1mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Spectrally resolved fluorescence lifetime imaging microscopy: Förster resonant energy transfer global analysis with a one- and two-exponential donor model

et al. 2011

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“…Regarding the capability of both LRP1 and APP to intracellularly bind Fe65, it is conceivable that the -secretase-shedded products LICD and AICD also compete for Fe65, suggesting that increased LICD presence in the nucleus intensely blocks APP signaling (Kinoshita et al 2003). The hypothesis that LRP1 is a substrate for BACE1 and might compete with APP for -secretase cleavage was further substantiated by recent Wndings, demonstrating that sAPP secretion could be reduced by co-overexpression of LRP1 (von Einem et al 2010).…”

Section: Lrp1 Function In App Metabolismmentioning

confidence: 91%

The role of lipoprotein receptors on the physiological function of APP

Wagner

Pietrzik

2011

Exp Brain Res

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In this review, we will primarily focus on the role of members of the low-density lipoprotein receptor (LDL-R) family that are involved in trafficking and processing of the amyloid precursor protein (APP). We will discuss the role of the LDL-receptor family members, low-density lipoprotein receptor-related protein 1 (LRP1), LRP1b, apolipoprotein E receptor 2, sortilin-related receptor (SorLA/LR11) and megalin/LRP2 on the physiological function of APP and its cellular localization. Additionally, we will focus on adaptor proteins that have been shown to influence the physiological function of LDL-R family members in combination with APP processing. The results in this review emphasize that the physiological function of APP cannot be explained by the focus on the APP protein alone but rather in combination with various direct or indirect interaction partners within the cellular environment.

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BACE1 regulates the proliferation and cellular functions of Schwann cells

Hou

Bastian

et al. 2017

Glia

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BACE1 is an indispensable enzyme for generating β-amyloid peptides, which are excessively accumulated in brains of Alzheimer’s patients. However, BACE1 is also required for proper myelination of peripheral nerves, as BACE1-null mice display hypomyelination. In order to determine the precise effects of BACE1 on myelination, here we have uncovered a role of BACE1 in the control of Schwann cell proliferation during development. We demonstrate that BACE1 regulates the cleavage of Jagged-1 and Delta-1, two membrane-bound ligands of Notch. BACE1 deficiency induces elevated Jag-Notch signaling activity, which in turn facilitates proliferation of Schwann cells. This increase in proliferation leads to shortened internodes and decreased Schmidt–Lanterman incisures. Functionally, evoked compound action potentials in BACE1-null nerves were significantly smaller and slower, with a clear decrease in excitability. BACE1-null nerves failed to effectively use lactate as an alternative energy source under conditions of increased physiological activity. Correlatively, BACE1-null mice showed reduced performance on rotarod tests. Collectively, our data suggest that BACE1 deficiency enhances proliferation of Schwann cell due to the elevated Jag1/Delta1-Notch signaling, but fails to myelinate axons efficiently due to impaired the neuregulin1-ErbB signaling, which has been documented.

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The role of low-density receptor-related protein 1 (LRP1) as a competitive substrate of the amyloid precursor protein (APP) for BACE1

Cited by 32 publications

References 38 publications

Spectrally resolved fluorescence lifetime imaging microscopy: Förster resonant energy transfer global analysis with a one- and two-exponential donor model

Spectrally resolved fluorescence lifetime imaging microscopy: Förster resonant energy transfer global analysis with a one- and two-exponential donor model

The role of lipoprotein receptors on the physiological function of APP

BACE1 regulates the proliferation and cellular functions of Schwann cells

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