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Presenilin‐1 Exists in Both Pre‐ and Post‐Golgi Compartments and Recycles Via COPI‐Coated Membranes
Abstract
Presenilin‐1 is involved in intramembrane proteolysis of various proteins, but its intracellular site of action has remained elusive. Here, we determined by quantitative immunogold‐electron microscopy that presenilin‐1 in Chinese hamster ovary cells is present in pre‐Golgi compartments as well as at the plasma membrane and endosomes. Notably, a high percentage of presenilin‐1 resides in COPI‐coated membranes between the endoplasmic reticulum and the Golgi complex, indicating significant recycling to the endoplasmic reticulum. By contrast, the inactive aspartate mutant presenilin‐1 D257A is relatively excluded from COPI‐coated membranes, concomitant with increased post‐Golgi levels. These data provide critical evidence for the scenario that the complex containing presenilin‐1 can serve as γ‐secretase at the plasma membrane or endosomes and suggest a role for COPI‐mediated retrograde transport in regulating post‐Golgi levels of presenilin‐1.
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“γ-secretase is also localized in the Golgi compartment (Rechards et al., 2003)”
From Distinct anterograde trafficking pathways of BACE1 and amyloid precursor protein from the TGN and the regulation of amyloid-β production (2020) · cites this paper as Rechards et al., 2003
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Metadata
- Authors
- Réchards, M., Xia, W., Oorschot, V. M. J., Selkoe, D. J., & Klumperman, J.
- Affiliations
- Utrecht University (NL)
- Brigham and Women's Hospital (US)
- Corresponding author
- Klumperman, Judith
- Venue
- Traffic
- Publisher
- Wiley
- Published
- 2003-07
- Volume
- 4
- Issue
- 8
- Pages
- 553-565
- ISSN
- 1398-9219 (ISSN-L)
- 1600-0854
- OpenAlex
- W2126704279
- Cited by
- 55
- References
- 2
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 1 · 2014: 4 · 2013: 3 · 2012: 3
- FWCI
- 2.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Traffic (publishedVersion)
- PubMed (publishedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Health Sciences › Medicine › Genetics (clinical) › Lysosomal Storage Disorders Research
- Keywords
- presenilin 1, gamma-secretase, retrograde transport, Golgi apparatus, endoplasmic reticulum, endosomes, plasma membrane, intramembrane proteolysis, subcellular localization, immunogold electron microscopy
- MeSH terms
- Animals, Cell Membrane, Cell Nucleus, Golgi Apparatus, Cricetinae, Humans, Membrane Proteins, Microscopy, Electron, Endosomes, CHO Cells, Amino Acid Substitution, trans-Golgi Network, COP-Coated Vesicles, Presenilin-1
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