2. Academic Validation
  3. Retriever is a multiprotein complex for retromer-independent endosomal cargo recycling

Retriever is a multiprotein complex for retromer-independent endosomal cargo recycling

  • Nat Cell Biol. 2017 Oct;19(10):1214-1225. doi: 10.1038/ncb3610.
Kerrie E McNally 1,  Rebecca Faulkner 2,  Florian Steinberg 3,  Matthew Gallon 1,  Rajesh Ghai 4,  David Pim 5,  Paul Langton 1,  Neil Pearson 1,  Chris M Danson 1,  Heike Nägele 3,  Lindsey L Morris 2,  Amika Singla 2,  Brittany L Overlee 6,  Kate J Heesom 7,  Richard Sessions 1,  Lawrence Banks 5,  Brett M Collins 4,  Imre Berger 1,  Daniel D Billadeau 6,  Ezra Burstein 2,  Peter J Cullen 1
Affiliations

Affiliations

  • 1 School of Biochemistry, Biomedical Sciences Building, University of Bristol, Bristol BS8 1TD, UK.
  • 2 Department of Internal Medicine and Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
  • 3 Center for Biological Systems Analysis, Albert Ludwigs Universitaet Freiburg, 79104 Freiburg, Germany.
  • 4 Institute for Molecular Bioscience, the University of Queensland, St. Lucia, Queensland 4072, Australia.
  • 5 International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34149 Trieste, Italy.
  • 6 Department of Biochemistry and Molecular Biology, and Department of Immunology, Mayo Clinic, Rochester, Minnesota 55905, USA.
  • 7 Proteomics Facility, School of Biochemistry, University of Bristol, Bristol BS8 1TD, UK.
PMID: 28892079 DOI: 10.1038/ncb3610
Abstract

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.

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