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

Kerrie E. McNally, Rebecca Faulkner, Florian Steinberg, Matthew Gallon, Rajesh Ghai, David Pim, Paul Langton, Neil Pearson, Chris M. Danson, Heike Nägele, Lindsey L. Morris, Amika Singla, Brittany L. Overlee, Kate J. Heesom, Richard Sessions, Lawrence Banks, Brett M. Collins, Imre Berger, Daniel D. Billadeau, Ezra BursteinPeter J. Cullen

Research output: Contribution to journalArticle (Academic Journal)

78 Citations (Scopus)
267 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)1214–1225
Number of pages12
JournalNature Cell Biology
Volume19
Issue number10
Early online date11 Sep 2017
DOIs
Publication statusPublished - 1 Oct 2017

Keywords

  • Cell biology
  • Endocytosis
  • Membrane trafficking

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  • Equipment

    Proteomics Facility

    Kate Heesom (Manager)

    Faculty of Life Sciences

    Facility/equipment: Facility

  • Cite this

    McNally, K. E., Faulkner, R., Steinberg, F., Gallon, M., Ghai, R., Pim, D., Langton, P., Pearson, N., Danson, C. M., Nägele, H., Morris, L. L., Singla, A., Overlee, B. L., Heesom, K. J., Sessions, R., Banks, L., Collins, B. M., Berger, I., Billadeau, D. D., ... Cullen, P. J. (2017). Retriever is a multiprotein complex for retromer-independent endosomal cargo recycling. Nature Cell Biology, 19(10), 1214–1225. https://doi.org/10.1038/ncb3610