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Endoplasmic reticulum retention of the γ‐secretase complex component Pen2 by Rer1
Author(s) -
Kaether Christoph,
Scheuermann Johanna,
Fassler Matthias,
Zilow Sonja,
Shirotani Keiro,
Valkova Christina,
Novak Bozidar,
Kacmar Slavomir,
Steiner Harald,
Haass Christian
Publication year - 2007
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7401027
Subject(s) - endoplasmic reticulum , microbiology and biotechnology , transmembrane domain , nicastrin , transmembrane protein , stim1 , er retention , chemistry , presenilin , golgi apparatus , biology , biochemistry , medicine , alzheimer's disease , receptor , mutant , gene , disease
γ‐Secretase is involved in the production of amyloid β‐peptide, which is the principal component of amyloid plaques in the brains of patients with Alzheimer disease. γ‐Secretase is a complex composed of presenilin (PS), nicastrin, anterior pharynx‐defective phenotype 1 (Aph1) and PS enhancer 2 (Pen2). We previously proposed a mechanism of complex assembly by which unassembled subunits are retained in the endoplasmic reticulum (ER) and only the fully assembled complex is exported from the ER. We have now identified Retention in endoplasmic reticulum 1 (Rer1) as a protein that is involved in the retention/retrieval of unassembled Pen2 to the ER. Direct binding of unassembled Pen2 to Rer1 is mediated by the first transmembrane domain of Pen2, and a conserved asparagine in this domain is required. Downregulation of Rer1 leads to increased surface localization of Pen2, whereas overexpression of Rer1 stabilizes unassembled Pen2. To our knowledge, Rer1 is the first identified interaction partner of mammalian transmembrane‐based retention/retrieval signals.