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A global analysis of SNX27–retromer assembly and cargo specificity reveals a function in glucose and metal ion transport

Nature Cell Biology volume 15, pages 461471 (2013) | Download Citation

  • An Erratum to this article was published on 03 June 2013
  • An Erratum to this article was published on 01 August 2014

This article has been updated


The PDZ-domain-containing sorting nexin 27 (SNX27) promotes recycling of internalized transmembrane proteins from endosomes to the plasma membrane by linking PDZ-dependent cargo recognition to retromer-mediated transport. Here, we employed quantitative proteomics of the SNX27 interactome and quantification of the surface proteome of SNX27- and retromer-suppressed cells to dissect the assembly of the SNX27 complex and provide an unbiased global view of SNX27-mediated sorting. Over 100 cell surface proteins, many of which interact with SNX27, including the glucose transporter GLUT1, the Menkes disease copper transporter ATP7A, various zinc and amino acid transporters, and numerous signalling receptors, require SNX27–retromer to prevent lysosomal degradation and maintain surface levels. Furthermore, we establish that direct interaction of the SNX27 PDZ domain with the retromer subunit VPS26 is necessary and sufficient to prevent lysosomal entry of SNX27 cargo. Our data identify the SNX27–retromer as a major endosomal recycling hub required to maintain cellular nutrient homeostasis.

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Change history

  • 23 April 2013

    In the version of this Article originally published, labels were incorrectly aligned to the blots in Fig. 6c,d. Furthermore, the middle initial of the author Elaine C. Thomas was missing.

  • 04 July 2014

    In the version of this Article originally published, an error in the journal production process led to the wrong image being used for 'SNX27KD' in Fig. 4b. The image has been corrected in all online versions of the Article.


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F.S. is a Royal Society Newton Fellow. M.G. and A.J.B. are supported by Wellcome Trust 4 Year PhD Studentships awarded through the Dynamic Cell Biology programme (083474). P.J.C. is supported by the Wellcome Trust (089928 and 085743) and the Royal Society. We thank M. Bass and D. Stephens for critical reading of the manuscript.

Author information


  1. The Henry Wellcome Integrated Signalling Laboratories, School of Biochemistry, University of Bristol, Bristol BS8 1TD, UK

    • Florian Steinberg
    • , Matthew Gallon
    • , Elaine C. Thomas
    • , Amanda J. Bell
    • , Jeremy M. Tavaré
    •  & Peter J. Cullen
  2. School of Biological Sciences, University of Bristol, Bristol BS8 1UG, UK

    • Mark Winfield
  3. Proteomics Facility, School of Biochemistry, University of Bristol, Bristol BS8 1TD, UK

    • Kate J. Heesom


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F.S., J.M.T. and P.J.C. designed the project; F.S., M.G., E.T. and A.J.B. performed the experiments; M.W. performed the bioinformatics; K.J.H. performed the proteomics; F.S., M.G. and P.J.C. wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Peter J. Cullen.

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