Premium
Endoplasmic Reticulum‐Localized Amyloid β‐Peptide is Degraded in the Cytosol by Two Distinct Degradation Pathways
Author(s) -
Schmitz Anton,
Schneider Andrea,
Kummer Markus P.,
Herzog Volker
Publication year - 2004
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1111/j.1600-0854.2004.00159.x
Subject(s) - endoplasmic reticulum associated protein degradation , endoplasmic reticulum , proteasome , biology , microbiology and biotechnology , cytosol , ubiquitin , secretory pathway , protein degradation , biochemistry , unfolded protein response , golgi apparatus , enzyme , gene
The paradigm of endoplasmic reticulum (ER)‐associated degradation (ERAD) holds that misfolded secretory and membrane proteins are translocated back to the cytosol and degraded by the proteasome in a coupled process. Analyzing the degradation of ER‐localized amyloid β‐peptide (Aβ), we found a divergence from this general model. Cell‐free reconstitution of the export in biosynthetically loaded ER‐derived brain microsomes showed that the export was mediated by the Sec61p complex and required a cytosolic factor but was independent of ATP. In contrast to the ERAD substrates known so far, the exported Aβ was degraded by both, a proteasome‐dependent and a proteasome‐independent pathway. RNA interference experiments in Aβ‐transfected cells identified the protease of the proteasome‐independent pathway as insulin‐degrading enzyme (IDE). The IDE‐mediated clearance mechanism for ER‐localized Aβ represents an as yet unknown type of ERAD which is not entirely dependent on the proteasome.