0000000000134268

AUTHOR

Anne M. Martin

showing 4 related works from this author

The Functional Role of the Second NPXY Motif of the LRP1 β-Chain in Tissue-type Plasminogen Activator-mediated Activation of N-Methyl-D-aspartate Rec…

2008

The low density lipoprotein receptor-related protein 1 (LRP1) emerges to play fundamental roles in cellular signaling pathways in the brain. One of its prominent ligands is the serine proteinase tissue-type plasminogen activator (tPA), which has been shown to act as a key activator of neuronal mitogen-activated protein kinase pathways via the N-methyl-D-aspartate (NMDA) receptor. However, here we set out to examine whether LRP1 and the NMDA receptor might eventually act in a combined fashion to mediate tPA downstream signaling. By blocking tPA from binding to LRP1 using the receptor-associated protein, we were able to completely inhibit NMDA receptor activation. Additionally, inhibition of …

Cell signalingAmino Acid MotifsPDZ domainIntracellular SpaceBiologyReceptors N-Methyl-D-AspartateBiochemistryProtein Structure SecondaryCell LineRats Sprague-DawleyMiceStructure-Activity RelationshipAnimalsHumansAmino Acid SequencePhosphorylationRNA Small InterferingReceptorProtein kinase AMolecular BiologyMitogen-Activated Protein Kinase 1NeuronsMitogen-Activated Protein Kinase 3Activator (genetics)Intracellular Signaling Peptides and ProteinsMembrane ProteinsReceptor Cross-TalkCell BiologyLRP1RatsCell biologyEnzyme ActivationBiochemistryTissue Plasminogen ActivatorDisks Large Homolog 4 ProteinCalciumDisks Large Homolog 4 ProteinGuanylate KinasesPlasminogen activatorLow Density Lipoprotein Receptor-Related Protein-1PlasmidsSignal TransductionJournal of Biological Chemistry
researchProduct

LRP1 modulates APP trafficking along early compartments of the secretory pathway

2008

The amyloid beta peptide (A beta) is a central player in Alzheimer's disease (AD) pathology. A beta liberation depends on APP cleavage by beta- and gamma-secretases. The low density lipoprotein receptor related protein 1 (LRP1) was shown to mediate APP processing at multiple steps. Newly synthesized LRP1 can interact with APP, implying an interaction between these two proteins early in the secretory pathway. We wanted to investigate whether LRP1 mediates APP trafficking along the secretory pathway, and, if so, whether it affects APP processing. Indeed, the early trafficking of APP within the secretory pathway is strongly influenced by its interaction with the C-terminal domain of LRP1. The …

GlycosylationAmyloid betaAmino Acid MotifsPlaque AmyloidCHO CellsSecretory pathwayTrafficinglcsh:RC321-571Amyloid beta-Protein PrecursorCricetulusAlzheimer DiseaseCricetinaemental disordersAmyloid precursor proteinAnimalsHumansReceptorlcsh:Neurosciences. Biological psychiatry. NeuropsychiatrySecretory pathwayNeuronsAmyloid beta-PeptidesbiologyLow density lipoprotein receptor related proteinBrainLRP1Cell CompartmentationProtein Structure TertiaryCell biologyProtein TransportNeurologyBiochemistryAlpha secretaseRetentionAmyloid precursor proteinLDL receptorbiology.proteinLiberationProtein Processing Post-TranslationalLow Density Lipoprotein Receptor-Related Protein-1Signal TransductionNeurobiology of Disease
researchProduct

Increased AICD generation does not result in increased nuclear translocation or activation of target gene transcription.

2008

A sequence of amyloid precursor protein (APP) cleavages culminates in the sequential release of the APP intracellular domain (AICD) and the amyloid beta peptide (Abeta) and/or p3 fragment. One of the environmental factors favouring the accumulation of AICD appears to be a rise in intracellular pH. Here we further identified the metabolism and subcellular localization of artificially expressed constructs under such conditions. We also co-examined the mechanistic lead up to the AICD accumulation and explored possible significances for its increased expression. We found that most of the AICD generated under pH neutralized conditions is likely cleaved from C83. While the AICD surplus was unable…

Transcriptional ActivationTranscription GeneticAmyloid betaActive Transport Cell NucleusCHO CellsModels BiologicalTransactivationAmyloid beta-Protein PrecursorCricetulusTranscription (biology)CricetinaeAmyloid precursor proteinAnimalsHumansLuciferaseCells CulturedRegulation of gene expressionCell NucleusbiologyCell BiologyHydrogen-Ion ConcentrationSubcellular localizationMolecular biologyCell biologyProtein Structure TertiaryCytosolbiology.proteinProtein Processing Post-TranslationalProtein BindingExperimental cell research
researchProduct

α-secretase mediated conversion of the amyloid precursor protein derived membrane stub C99 to C83 limits Aβ generation

2009

The Swedish mutation within the amyloid precursor protein (APP) causes early-onset Alzheimer's disease due to increased cleavage of APP by BACE1. While beta-secretase shedding of Swedish APP (APPswe) largely results from an activity localized in the late secretory pathway, cleavage of wild-type APP occurs mainly in endocytic compartments. However, we show that liberation of Abeta from APPswe is still dependent on functional internalization from the cell surface. Inspite the unchanged overall beta-secretase cleaved soluble APP released from APP(swe) secretion, mutations of the APPswe internalization motif strongly reduced C99 levels and substantially decreased Abeta secretion. We point out t…

medicine.medical_specialtymedia_common.quotation_subjectEndocytic cycleCHO CellsTransfectionBiochemistryAmyloid beta-Protein PrecursorCellular and Molecular NeuroscienceCricetulusCricetinaeInternal medicinemental disordersmedicineAmyloid precursor proteinAnimalsHumansBiotinylationProtein Interaction Domains and MotifsSecretionInternalizationSecretory pathwaymedia_commonAmyloid beta-PeptidesbiologyChemistryP3 peptidePeptide FragmentsCell biologyEndocrinologyGene Expression RegulationAlpha secretaseMutationbiology.proteinAmyloid Precursor Protein SecretasesAmyloid precursor protein secretaseJournal of Neurochemistry
researchProduct