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GGA proteins regulate retrograde transport of BACE1 from endosomes to the trans-Golgi network

Wahle, Tina, Prager, Kai, Raffler, Nikolai, Haass, Christian, Famulok, Michael, Walter, Jochen·2005·Molecular and Cellular Neuroscience
DOI 10.1016/j.mcn.2005.03.014
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Abstract

Golgi-localized, gamma ear-containing, ADP ribosylation factor-binding (GGA) proteins have been shown to be implicated in the sorting of cargo proteins from the trans-Golgi network (TGN) to endosomal compartments. GGAs directly bind to DXXLL motifs in the cytoplasmic domains of cargo proteins. The Alzheimer-associated beta-secretase BACE1 also interacts with GGA proteins, but the functional relevance of this interaction was unknown. Here, we show that GGA1 regulates the retrograde transport of internalized BACE1 from endosomal compartments to the TGN by direct interaction in a phosphorylation-dependent manner. While phosphorylated BACE1 is efficiently transported from endosomes to the TGN, non-phosphorylated BACE1 enters a direct recycling route to the cell surface. Our data indicate that GGA proteins are not only involved in the sorting at the TGN but also mediate the retrograde transport of cargo proteins from endosomes to the TGN.

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  • GGA proteins interact with the cytoplasmic domain of BACE1 in a phosphorylation-state-dependent manner and regulate the endocytic trafficking of this protease.

    “GGA proteins have been shown to interact with the cytoplasmic domain of BACE1 in a phosphorylation-state-dependent manner and to regulate the endocytic trafficking of this protease (He et al., 2002(He et al., , 2003(He et al., , 2005;;von Arnim et al., 2004;Wahle et al., 2005).”

    From GGA1 Is Expressed in the Human Brain and Affects the Generation of Amyloid β-Peptide (2006) · cites this paper as Wahle et al., 2005

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Metadata

Authors
Wahle, T., Prager, K., Raffler, N., Haass, C., Famulok, M., & Walter, J.
Venue
Molecular and Cellular Neuroscience
Publisher
Elsevier BV
Published
2005-07
Volume
29
Issue
3
Pages
453-461
ISSN
1044-7431
DOI
10.1016/j.mcn.2005.03.014
Cited by
102
References
0
Language
en
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)

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