Protein networks supporting AP-3 function in targeting lysosomal membrane proteins
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
Abstract
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 ≈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.
Details
Original language | English |
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Pages (from-to) | 1942-1951 |
Number of pages | 10 |
Journal | Molecular Biology of the Cell |
Volume | 19 |
Issue number | 5 |
Publication status | Published - May 2008 |
Peer-reviewed | Yes |
External IDs
PubMed | 18287518 |
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