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          Institute: MPI für molekulare Zellbiologie und Genetik     Collection: Publikationen MPI-CBG 2008     Display Documents

ID: 414397.0, MPI für molekulare Zellbiologie und Genetik / Publikationen MPI-CBG 2008
Protein networks supporting AP-3 function in targeting lysosomal membrane proteins
Authors:Baust, Thorsten; Anitei, Mihaela; Czupalla, Cornelia; Parshyna, Iryna; Bourel, Line; Thiele, Christoph; Krause, Eberhard; Hoflack, Bernard
Date of Publication (YYYY-MM-DD):2008
Title of Journal:Molecular Biology of the Cell
Issue / Number:5
Start Page:1942
End Page:1951
Copyright:not available
Audience:Experts Only
Intended Educational Use:No
Abstract / Description:The AP-3 adaptor complex targets selected transmembrane proteins to lysosomes and lysosome-related organelles. We reconstituted its preferred interaction with liposomes containing the ADP ribosylation factor (ARF)-1 guanosine triphosphatase (GTPase), specific cargo tails, and phosphatidylinositol-3 phosphate, and then we performed a proteomic screen to identify new proteins supporting its sorting function. We identified approximately 30 proteins belonging to three networks regulating either AP-3 coat assembly or septin polymerization or Rab7-dependent lysosomal transport. RNA interference shows that, among these proteins, the ARF-1 exchange factor brefeldin A-inhibited exchange factor 1, the ARF-1 GTPase-activating protein 1, the Cdc42-interacting Cdc42 effector protein 4, an effector of septin-polymerizing GTPases, and the phosphatidylinositol-3 kinase IIIC3 are key components regulating the targeting of lysosomal membrane proteins to lysosomes in vivo. This analysis reveals that these proteins, together with AP-3, play an essential role in protein sorting at early endosomes, thereby regulating the integrity of these organelles.
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Communicated by:n.n.
Affiliations:MPI f�r molekulare Zellbiologie und Genetik
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