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Sortilin and retromer mediate retrograde transport of Glut4 in 3T3-L1 adipocytes

Sortilin is a multiligand sorting receptor responsible for the anterograde transport of lysosomal enzymes and substrates. Here we demonstrate that sortilin is also involved in retrograde protein traffic. In cultured 3T3-L1 adipocytes, sortilin together with retromer rescues Glut4 from degradation in...

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Autores principales: Pan, Xiang, Zaarur, Nava, Singh, Maneet, Morin, Peter, Kandror, Konstantin V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5469609/
https://www.ncbi.nlm.nih.gov/pubmed/28450454
http://dx.doi.org/10.1091/mbc.E16-11-0777
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author Pan, Xiang
Zaarur, Nava
Singh, Maneet
Morin, Peter
Kandror, Konstantin V.
author_facet Pan, Xiang
Zaarur, Nava
Singh, Maneet
Morin, Peter
Kandror, Konstantin V.
author_sort Pan, Xiang
collection PubMed
description Sortilin is a multiligand sorting receptor responsible for the anterograde transport of lysosomal enzymes and substrates. Here we demonstrate that sortilin is also involved in retrograde protein traffic. In cultured 3T3-L1 adipocytes, sortilin together with retromer rescues Glut4 from degradation in lysosomes and retrieves it to the TGN, where insulin-­responsive vesicles are formed. Mechanistically, the luminal Vps10p domain of sortilin interacts with the first luminal loop of Glut4, and the cytoplasmic tail of sortilin binds to retromer. Ablation of the retromer does not affect insulin signaling but decreases the stability of sortilin and Glut4 and blocks their entry into the small vesicular carriers. As a result, Glut4 cannot reach the insulin-responsive compartment, and insulin-stimulated glucose uptake in adipocytes is suppressed. We suggest that sortilin- and retromer-mediated Glut4 retrieval from endosomes may represent a step in the Glut4 pathway vulnerable to the development of insulin resistance and diabetes.
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spelling pubmed-54696092017-08-30 Sortilin and retromer mediate retrograde transport of Glut4 in 3T3-L1 adipocytes Pan, Xiang Zaarur, Nava Singh, Maneet Morin, Peter Kandror, Konstantin V. Mol Biol Cell Articles Sortilin is a multiligand sorting receptor responsible for the anterograde transport of lysosomal enzymes and substrates. Here we demonstrate that sortilin is also involved in retrograde protein traffic. In cultured 3T3-L1 adipocytes, sortilin together with retromer rescues Glut4 from degradation in lysosomes and retrieves it to the TGN, where insulin-­responsive vesicles are formed. Mechanistically, the luminal Vps10p domain of sortilin interacts with the first luminal loop of Glut4, and the cytoplasmic tail of sortilin binds to retromer. Ablation of the retromer does not affect insulin signaling but decreases the stability of sortilin and Glut4 and blocks their entry into the small vesicular carriers. As a result, Glut4 cannot reach the insulin-responsive compartment, and insulin-stimulated glucose uptake in adipocytes is suppressed. We suggest that sortilin- and retromer-mediated Glut4 retrieval from endosomes may represent a step in the Glut4 pathway vulnerable to the development of insulin resistance and diabetes. The American Society for Cell Biology 2017-06-15 /pmc/articles/PMC5469609/ /pubmed/28450454 http://dx.doi.org/10.1091/mbc.E16-11-0777 Text en © 2017 Pan et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Pan, Xiang
Zaarur, Nava
Singh, Maneet
Morin, Peter
Kandror, Konstantin V.
Sortilin and retromer mediate retrograde transport of Glut4 in 3T3-L1 adipocytes
title Sortilin and retromer mediate retrograde transport of Glut4 in 3T3-L1 adipocytes
title_full Sortilin and retromer mediate retrograde transport of Glut4 in 3T3-L1 adipocytes
title_fullStr Sortilin and retromer mediate retrograde transport of Glut4 in 3T3-L1 adipocytes
title_full_unstemmed Sortilin and retromer mediate retrograde transport of Glut4 in 3T3-L1 adipocytes
title_short Sortilin and retromer mediate retrograde transport of Glut4 in 3T3-L1 adipocytes
title_sort sortilin and retromer mediate retrograde transport of glut4 in 3t3-l1 adipocytes
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5469609/
https://www.ncbi.nlm.nih.gov/pubmed/28450454
http://dx.doi.org/10.1091/mbc.E16-11-0777
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