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Imaging the Intracellular Trafficking of APP with Photoactivatable GFP
Published on: October 17, 2015
Presenilin-1 exists in both pre- and post-Golgi compartments and recycles via COPI-coated membranes
Marloes Réchards1, Weiming Xia, Viola M J Oorschot
1Department of Cell Biology, University Medical Center and Institute for Biomembranes, Center for Biomedical Genetics, Utrecht University, 3584 CX Utrecht, The Netherlands.
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-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 gamma-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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