Presenilin-1 exist in both pre- and post-golgi compartments and recycles via COPI-coated membranes

Marloes Réchards, Weiming Xia, Viola M.J. Oorschot, Dennis J. Selkoe, Judith Klumperman

Research output: Contribution to journalReview articlepeer-review

51 Scopus citations


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-1D257A 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.

Original languageEnglish (US)
Pages (from-to)553-565
Number of pages13
Issue number8
StatePublished - Aug 1 2003


  • Alzheimer
  • COPI
  • Immuno-electron microscopy
  • Intracellular traffic
  • Presenilin

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Structural Biology
  • Molecular Biology
  • Genetics


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