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PMID: 23563491 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Nature cell biology ·Vol. 15 ·No. 5 ·2013-05-00 ·Pages 461-71

Steinberg F, Gallon M, Winfield M, Thomas EC, Bell AJ, Heesom KJ, Tavaré JM, Cullen PJ

Abstract

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.

MeSH Terms
Adenosine Triphosphatases/genetics,metabolism Blotting, Western Cation Transport Proteins/genetics,metabolism Computational Biology/methods Copper-Transporting ATPases Culture Media/metabolism Glucose/metabolism Glucose Transporter Type 1/genetics,metabolism HeLa Cells Humans Ion Transport Isotope Labeling/methods Lysosomes/metabolism Multiprotein Complexes/metabolism PDZ Domains Protein Folding Protein Interaction Mapping Protein Transport Proteolysis Proteomics/methods RNA, Small Interfering/genetics,metabolism Receptor, Platelet-Derived Growth Factor beta/genetics,metabolism Receptors, TNF-Related Apoptosis-Inducing Ligand/genetics,metabolism Sorting Nexins/analysis,genetics,metabolism Vesicular Transport Proteins/genetics,metabolism
Chemicals
Cation Transport Proteins Culture Media Glucose Transporter Type 1 Multiprotein Complexes RNA, Small Interfering Receptors, TNF-Related Apoptosis-Inducing Ligand SLC2A1 protein, human SNX27 protein, human Sorting Nexins TNFRSF10A protein, human VPS26A protein, human VPS35 protein, human Vesicular Transport Proteins Receptor, Platelet-Derived Growth Factor beta Adenosine Triphosphatases ATP7A protein, human Copper-Transporting ATPases Glucose
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Steinberg Florian
The Henry Wellcome Integrated Signalling Laboratories, School of Biochemistry, University of Bristol, Bristol BS8 1TD, UK.
Gallon Matthew
Winfield Mark
Thomas Elaine C
Bell Amanda J
Heesom Kate J
Tavaré Jeremy M
Cullen Peter J
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Article Info
Journal
Nature cell biology
Abbr.
Nat Cell Biol
ISSN
1476-4679
DOI
10.1038/ncb2721
Published
2013-05-00
Epub
2013-00-07
Pages
461-71
Language
English
Region
England
NLM ID
100890575
PMCID
PMC4052425
Subset
IM
Grants
Wellcome Trust · 089928 · United Kingdom
British Heart Foundation · PG/10/008/28186 · United Kingdom
Wellcome Trust · 085743 · United Kingdom
Corrections
ErratumIn
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CommentIn
PMID: 23636423
External Links
PubMed source DOI: 10.1038/ncb2721 PMC Full Text View journal details
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