ArticleThe Journal of cell biology2002
Presenilin-1 affects trafficking and processing of betaAPP and is targeted in a complex with nicastrin to the plasma membrane.
Article in The Journal of cell biology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
What it found
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Who cites it
59 citing papers in PubMed, 189 citations in OpenAlex.
- Presenilin 1 Modulates Acetylcholinesterase Trafficking and Maturation.International journal of molecular sciences · 2023Article
- Class II phosphatidylinositol 3-kinase-C2α is essential for Notch signaling by regulating the endocytosis of γ-secretase in endothelial cells.Scientific reports · 2021Article
- Super-resolution microscopy reveals majorly mono- and dimeric presenilin1/γ-secretase at the cell surface.eLife · 2020Article
- Review
- Zinc and Copper Differentially Modulate Amyloid Precursor Protein Processing by γ-Secretase and Amyloid-β Peptide Production.The Journal of biological chemistry · 2017Article
- The Role of Presenilin in Protein Trafficking and Degradation-Implications for Metal Homeostasis.Journal of molecular neuroscience : MN · 2016Review
- Differential transgene expression patterns in Alzheimer mouse models revealed by novel human amyloid precursor protein-specific antibodies.Aging cell · 2016Article
- Presenilin 1 and Presenilin 2 Target γ-Secretase Complexes to Distinct Cellular Compartments.The Journal of biological chemistry · 2016Article
- Physical and functional interaction between the α- and γ-secretases: A new model of regulated intramembrane proteolysis.The Journal of cell biology · 2015Article
- Twenty Years of Presenilins--Important Proteins in Health and Disease.Molecular medicine (Cambridge, Mass.) · 2015Article
- Arf6 controls beta-amyloid production by regulating macropinocytosis of the Amyloid Precursor Protein to lysosomes.Molecular brain · 2015Article
- Targeting the γ-/β-secretase interaction reduces β-amyloid generation and ameliorates Alzheimer's disease-related pathogenesis.Cell discovery · 2015Article
- The Amyloid Precursor Protein is rapidly transported from the Golgi apparatus to the lysosome and where it is processed into beta-amyloid.Molecular brain · 2014Article
- Sequential proteolytic processing of the triggering receptor expressed on myeloid cells-2 (TREM2) protein by ectodomain shedding and γ-secretase-dependent intramembranous cleavage.The Journal of biological chemistry · 2013Article
- Nicastrin overexpression in transgenic mice induces aberrant behavior and APP processing.Molecular neurobiology · 2013Article
- Structural biology of presenilins and signal peptide peptidases.The Journal of biological chemistry · 2013Review
- The ubiquitin ligase synoviolin up-regulates amyloid β production by targeting a negative regulator of γ-secretase, Rer1, for degradation.The Journal of biological chemistry · 2012Article
- Retention in endoplasmic reticulum 1 (RER1) modulates amyloid-β (Aβ) production by altering trafficking of γ-secretase and amyloid precursor protein (APP).The Journal of biological chemistry · 2012Article
- Trafficking and proteolytic processing of APP.Cold Spring Harbor perspectives in medicine · 2012Review
- Neutralization of the γ-secretase activity by monoclonal antibody against extracellular domain of nicastrin.Oncogene · 2012Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Amyloid beta-peptide (Abeta) is generated by the consecutive cleavages of beta- and gamma-secretase. The intramembraneous gamma-secretase cleavage critically depends on the activity of presenilins (PS1 and PS2). Although there is evidence that PSs are aspartyl proteases with gamma-secretase activity, it remains controversial whether their subcellular localization overlaps with the cellular sites of Abeta production. We now demonstrate that biologically active GFP-tagged PS1 as well as endogenous PS1 are targeted to the plasma membrane (PM) of living cells. On the way to the PM, PS1 binds to nicastrin (Nct), an essential component of the gamma-secretase complex. This complex is targeted through the secretory pathway where PS1-bound Nct becomes endoglycosidase H resistant. Moreover, surface-biotinylated Nct can be coimmunoprecipitated with PS1 antibodies, demonstrating that this complex is located to cellular sites with gamma-secretase activity. Inactivating PS1 or PS2 function by mutagenesis of one of the critical aspartate residues or by gamma-secretase inhibitors results in delayed reinternalization of the beta-amyloid precursor protein and its accumulation at the cell surface. Our data suggest that PS is targeted as a biologically active complex with Nct through the secretory pathway to the cell surface and suggest a dual function of PS in gamma-secretase processing and in trafficking.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.