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

KE McNally, R Faulkner, F Steinberg, M Gallon… - Nature cell …, 2017 - nature.com
KE McNally, R Faulkner, F Steinberg, M Gallon, R Ghai, D Pim, P Langton, N Pearson
Nature cell biology, 2017nature.com
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 …
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.
nature.com