Journal article

Retromer- and WASH-dependent sorting of nutrient transporters requires a multivalent interaction network with ANKRD50

  • Kvainickas, Arunas Center for Biological Systems Analysis (ZBSA), Albert Ludwigs Universitaet, Freiburg, Germany - Faculty of Biology, Freiburg, Germany
  • Orgaz, Ana Jimenez Center for Biological Systems Analysis (ZBSA), Albert Ludwigs Universitaet, Freiburg, Germany - Faculty of Biology, Freiburg, Germany
  • Nägele, Heike Center for Biological Systems Analysis (ZBSA), Albert Ludwigs Universitaet, Freiburg, Germany - Faculty of Biology, Freiburg, Germany
  • Diedrich, Britta Center for Biological Systems Analysis (ZBSA), Albert Ludwigs Universitaet, Freiburg, Germany - Faculty of Biology, Freiburg, Germany
  • Heesom, Kate J. School of Biochemistry, Bristol University, UK
  • Dengjel, Jörn Department of Biology, University of Fribourg, Switzerland
  • Cullen, Peter J. School of Biochemistry, Bristol University, UK
  • Steinberg, Florian Center for Biological Systems Analysis (ZBSA), Albert Ludwigs Universitaet, Freiburg, Germany - Faculty of Biology, Freiburg, Germany
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    15.01.2017
Published in:
  • J Cell Sci. - 2017, vol. 130, no. 2, p. 382–395
English Retromer and the associated actin-polymerizing WASH complex are essential for the endocytic recycling of a wide range of integral membrane proteins. A hereditary Parkinson's-disease-causing point mutation (D620N) in the retromer subunit VPS35 perturbs retromer's association with the WASH complex and also with the uncharacterized protein ankyrin-repeat-domain-containing protein 50 (ANKRD50). Here, we firmly establish ANKRD50 as a new and essential component of the SNX27– retromer–WASH super complex. Depletion of ANKRD50 in HeLa or U2OS cells phenocopied the loss of endosome-to-cell-surface recycling of multiple transmembrane proteins seen upon suppression of SNX27, retromer or WASH- complex components. Mass-spectrometry-based quantification of the cell surface proteome of ANKRD50-depleted cells identified amino acid transporters of the SLC1A family, among them SLC1A4, as additional cargo molecules that depend on ANKRD50 and retromer for their endocytic recycling. Mechanistically, we show that ANKRD50 simultaneously engages multiple parts of the SNX27–retromer–WASH complex machinery in a direct and co-operative interaction network that is needed to efficiently recycle the nutrient transporters GLUT1 (also known as SLC2A1) and SLC1A4, and potentially many other surface proteins.
Faculty
Faculté des sciences et de médecine
Department
Département de Biologie
Language
  • English
Classification
Biological sciences
License
License undefined
Identifiers
Persistent URL
https://folia.unifr.ch/unifr/documents/305371
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