Cited by 355Alzheimer's disease research and treatmentsCellular transport and secretionNeuroscience and Neuropharmacology Research

Effects of PS1 Deficiency on Membrane Protein Trafficking in Neurons

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Naruse, Satoshi, Thinakaran, Gopal, Luo, Jin-Jun, Kusiak, John W, Tomita, Taisuke, Iwatsubo, Takeshi, Qian, Xiaozhong, Ginty, David D +4 more·1998·Neuron

Abstract

We have examined the trafficking and metabolism of the beta-amyloid precursor protein (APP), an APP homolog (APLP1), and TrkB in neurons that lack PS1. We report that PS1-deficient neurons fail to secrete Abeta, and that the rate of appearance of soluble APP derivatives in the conditioned medium is increased. Remarkably, carboxyl-terminal fragments (CTFs) derived from APP and APLP1 accumulate in PS1-deficient neurons. Hence, PS1 plays a role in promoting intramembrane cleavage and/or degradation of membrane-bound CTFs. Moreover, the maturation of TrkB and BDNF-inducible TrkB autophosphorylation is severely compromised in neurons lacking PS1. We conclude that PS1 plays an essential role in modulating trafficking and metabolism of a selected set of membrane and secretory proteins in neurons.

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  • Tail biopsy samples were used to isolate DNA to confirm the genotype of the strain using previously established primers by PCR.

    “Tail biopsy samples were used to isolate DNA to confirm the genotype of the strain using previously established primers by PCR93–95.”

    From Serum amyloid P secreted by bone marrow adipocytes drives skeletal amyloidosis (2025) · cites this paper as [95]

    The Results describe cultures from embryos with different PS1 genotypes, but do not say how those genotypes were determined. Searches for tail biopsy, DNA isolation, PCR, and genotyping primers found no passage describing the claimed procedure. (LLM, conf=0.74)

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Research works printed but not linked: 2

  1. [4]4. Chao, M.V Neurotrophin receptorsa window into neuronal differentiation Neuron. 1992; 9:583-593 Full Text (PDF) Scopus (710) PubMed Google Scholar
  2. [18]18. Kim, K.S ∙ Wen, G.Y ∙ Bancher, C ... Detection and quantitation of amyloid B-peptide with 2 monoclonal antibodies Neurosci. Res. Commun. 1990; 7:113-122 Google Scholar

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Authors
Naruse, S., Thinakaran, G., Luo, J.-J., Kusiak, J. W., Tomita, T., Iwatsubo, T., Qian, X., Ginty, D. D., Price, D. L., Borchelt, D. R., Wong, P. C., & Sisodia, S. S.
Affiliations
  • University of Chicago (US)
  • Johns Hopkins University (US)
  • National Institute on Aging (US)
  • The University of Tokyo (JP)
Corresponding author
Sisodia, Sangram S
Venue
Neuron
Publisher
Elsevier BV
Published
1998-11
Volume
21
Issue
5
Pages
1213-1221
ISSN
0896-6273 (ISSN-L)
OpenAlex
W1994453752
Cited by
355
References
43
Citations by year
2026: 1 · 2025: 3 · 2024: 2 · 2023: 3 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 2 · 2017: 4 · 2016: 5 · 2015: 4 · 2014: 4 · 2013: 12 · 2012: 7
FWCI
22.15
Type
journal article
Language
en
Open access
Locations
  • Neuron (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • National Institute on Aging (1PO1 AG 14248, P50AG005146, P01AG014248, AG 05146)
  • National Institute of Neurological Disorders and Stroke (NS-20471)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
presenilin 1, APP, APLP1, amyloid-beta, carboxyl-terminal fragment, membrane protein trafficking, TrkB, brain-derived neurotrophic factor, autophosphorylation, intramembrane cleavage, protein degradation, Alzheimer's disease, neurons
MeSH terms
Alzheimer Disease, Animals, Cells, Cultured, Cerebral Cortex, Fetus, Membrane Proteins, Molecular Sequence Data, Neurons, Amyloid beta-Protein Precursor, Mice, Knockout, Mice, Presenilin-1

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