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EMBO reports 8, 8, 743–748 (2007)
doi:10.1038/sj.embor.7401027
AOP Published online: 6 July 2007
Endoplasmic reticulum retention of the  -secretase complex component Pen2 by Rer1
Christoph Kaether1, 2, Johanna Scheuermann1, Matthias Fassler2, Sonja Zilow1, Keiro Shirotani1, Christina Valkova2, Bozidar Novak1, Slavomir Kacmar2, Harald Steiner1 & Christian Haass1
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1 Laboratory for Alzheimer's and Parkinson's Disease Research, Department of Biochemistry, Center For Integrated Protein Science Munich and Adolf-Butenandt-Institute, Ludwig-Maximilians-Universität, München 80336, Germany
2 Leibniz Institute for Age Research-Fritz Lipmann Institute, Jena 07743, Germany
Received 8 January 2007; Accepted 4 June 2007; Published online 6 July 2007.
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Abstract
-Secretase is involved in the production of amyloid  -peptide, which is the principal component of amyloid plaques in the brains of patients with Alzheimer disease. -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.
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