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

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)1214–1225
Number of pages12
JournalNature Cell Biology
Volume19
Issue number10
DOIs
DateAccepted/In press - 10 Aug 2017
DatePublished (current) - 11 Sep 2017

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.

    Research areas

  • Cell biology, Endocytosis, Membrane trafficking

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    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Springer Nature at https://www.nature.com/articles/ncb3610#abstract. Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 10 MB, PDF document

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