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Presenilin‐1 Exists in Both Pre‐ and Post‐Golgi Compartments and Recycles Via COPI‐Coated Membranes
Author(s) -
Réchards Marloes,
Xia Weiming,
Oorschot Viola M. J.,
Selkoe Dennis J.,
Klumperman Judith
Publication year - 2003
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1034/j.1600-0854.2003.t01-1-00114.x
Subject(s) - golgi apparatus , endoplasmic reticulum , copi , endosome , microbiology and biotechnology , biology , presenilin , endomembrane system , brefeldin a , secretory pathway , intracellular , alzheimer's disease , medicine , disease , pathology
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.