1. Masking of Transmembrane-Based Retention Signals Controls ER Export of γ-Secretase.
- Author
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Fassler, Matthias, Zocher, Michael, Klare, Sebastian, de la Fuente, Alerie Guzman, Scheuermann, Johanna, Capell, Anja, Haass, Christian, Valkova, Christina, Veerappan, Anbazhagan, Schneider, Dirk, and Kaether, Christoph
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ENDOPLASMIC reticulum , *CELL membranes , *ALZHEIMER'S disease , *ORGANELLES , *BIOLOGICAL membranes - Abstract
γ-Secretase is critically involved in the Notch pathway and in Alzheimer's disease. The four subunits of γ-secretase assemble in the endoplasmic reticulum (ER) and unassembled subunits are retained/retrieved to the ER by specific signals. We here describe a novel ER-retention/retrieval signal in the transmembrane domain (TMD) 4 of presenilin 1, a subunit of γ-secretase. TMD4 also is essential for complex formation, conferring a dual role for this domain. Likewise, TMD1 of Pen2 is bifunctional as well. It carries an ER-retention/retrieval signal and is important for complex assembly by binding to TMD4. The two TMDs directly interact with each other and mask their respective ER-retention/retrieval signals, allowing surface transport of reporter proteins. Our data suggest a model how assembly of Pen2 into the nascent γ-secretase complex could mask TMD-based ER-retention/retrieval signals to allow plasma membrane transport of fully assembled γ-secretase. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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