Retriever is a multiprotein complex for retromer-independent endosomal cargo recycling
Retriever is a multiprotein complex for retromer-independent endosomal cargo recycling
Following endocytosis into the endosomal network, integral membrane proteins undergo sorting for lysosomal degradation or are retrieved and recycled back to the cell surface. Here we describe the discovery of an ancient and conserved multiprotein complex that orchestrates cargo retrieval and recycling and, importantly, is biochemically and functionally distinct from the established retromer pathway. We have called this complex 'retriever'; it is a heterotrimer composed of DSCR3, C16orf62 and VPS29, and bears striking similarity to retromer. We establish that retriever associates with the cargo adaptor sorting nexin 17 (SNX17) and couples to CCC (CCDC93, CCDC22, COMMD) and WASH complexes to prevent lysosomal degradation and promote cell surface recycling of α5β1 integrin. Through quantitative proteomic analysis, we identify over 120 cell surface proteins, including numerous integrins, signalling receptors and solute transporters, that require SNX17-retriever to maintain their surface levels. Our identification of retriever establishes a major endosomal retrieval and recycling pathway.
- International Centre for Genetic Engineering and Biotechnology Italy
- The University of Texas Southwestern Medical Center United States
- Mayo Clinic United States
- University of Queensland Australia
- University of Bristol United Kingdom
Models, Molecular, 570, Cell biology, Membrane trafficking, Endosomes, 333, 1307 Cell Biology, Animals, Genetically Modified, 616, Animals, Drosophila Proteins, Humans, Protein Interaction Domains and Motifs, Protein Stability, Cell Membrane, Intracellular Signaling Peptides and Proteins, Proteins, Cell Biology, Endocytosis, Neoplasm Proteins, Kinetics, Protein Transport, Drosophila melanogaster, HEK293 Cells, Multiprotein Complexes, Proteolysis, synthetic biology, /dk/atira/pure/core/keywords/biodesign_SRI; name=Bristol BioDesign Institute, HeLa Cells, Protein Binding
Models, Molecular, 570, Cell biology, Membrane trafficking, Endosomes, 333, 1307 Cell Biology, Animals, Genetically Modified, 616, Animals, Drosophila Proteins, Humans, Protein Interaction Domains and Motifs, Protein Stability, Cell Membrane, Intracellular Signaling Peptides and Proteins, Proteins, Cell Biology, Endocytosis, Neoplasm Proteins, Kinetics, Protein Transport, Drosophila melanogaster, HEK293 Cells, Multiprotein Complexes, Proteolysis, synthetic biology, /dk/atira/pure/core/keywords/biodesign_SRI; name=Bristol BioDesign Institute, HeLa Cells, Protein Binding
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