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A heterodimeric SNX4–SNX7 SNX-BAR autophagy complex coordinates ATG9A trafficking for efficient autophagosome assembly
The sorting nexins (SNXs) are a family of peripheral membrane proteins that direct protein trafficking decisions within the endocytic network. Emerging evidence in yeast and mammalian cells implicates a subgroup of SNXs in selective and non-selective forms of autophagy. Using siRNA and CRISPR-Cas9,...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists Ltd
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375690/ https://www.ncbi.nlm.nih.gov/pubmed/32513819 http://dx.doi.org/10.1242/jcs.246306 |
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author | Antón, Zuriñe Betin, Virginie M. S. Simonetti, Boris Traer, Colin J. Attar, Naomi Cullen, Peter J. Lane, Jon D. |
author_facet | Antón, Zuriñe Betin, Virginie M. S. Simonetti, Boris Traer, Colin J. Attar, Naomi Cullen, Peter J. Lane, Jon D. |
author_sort | Antón, Zuriñe |
collection | PubMed |
description | The sorting nexins (SNXs) are a family of peripheral membrane proteins that direct protein trafficking decisions within the endocytic network. Emerging evidence in yeast and mammalian cells implicates a subgroup of SNXs in selective and non-selective forms of autophagy. Using siRNA and CRISPR-Cas9, we demonstrate that the SNX-BAR protein SNX4 is needed for efficient LC3 (also known as MAP1LC3) lipidation and autophagosome assembly in mammalian cells. SNX-BARs exist as homo- and hetero-dimers, and we show that SNX4 forms functional heterodimers with either SNX7 or SNX30 that associate with tubulovesicular endocytic membranes. Detailed image-based analysis during the early stages of autophagosome assembly reveals that SNX4–SNX7 is an autophagy-specific SNX-BAR heterodimer, required for efficient recruitment and/or retention of core autophagy regulators at the nascent isolation membrane. SNX4 partially colocalises with juxtanuclear ATG9A-positive membranes, with our data linking the autophagy defect upon SNX4 disruption to the mis-trafficking and/or retention of ATG9A in the Golgi region. Taken together, our findings show that the SNX4–SNX7 heterodimer coordinates ATG9A trafficking within the endocytic network to establish productive autophagosome assembly sites, thus extending knowledge of SNXs as positive regulators of autophagy. |
format | Online Article Text |
id | pubmed-7375690 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | The Company of Biologists Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-73756902020-08-05 A heterodimeric SNX4–SNX7 SNX-BAR autophagy complex coordinates ATG9A trafficking for efficient autophagosome assembly Antón, Zuriñe Betin, Virginie M. S. Simonetti, Boris Traer, Colin J. Attar, Naomi Cullen, Peter J. Lane, Jon D. J Cell Sci Research Article The sorting nexins (SNXs) are a family of peripheral membrane proteins that direct protein trafficking decisions within the endocytic network. Emerging evidence in yeast and mammalian cells implicates a subgroup of SNXs in selective and non-selective forms of autophagy. Using siRNA and CRISPR-Cas9, we demonstrate that the SNX-BAR protein SNX4 is needed for efficient LC3 (also known as MAP1LC3) lipidation and autophagosome assembly in mammalian cells. SNX-BARs exist as homo- and hetero-dimers, and we show that SNX4 forms functional heterodimers with either SNX7 or SNX30 that associate with tubulovesicular endocytic membranes. Detailed image-based analysis during the early stages of autophagosome assembly reveals that SNX4–SNX7 is an autophagy-specific SNX-BAR heterodimer, required for efficient recruitment and/or retention of core autophagy regulators at the nascent isolation membrane. SNX4 partially colocalises with juxtanuclear ATG9A-positive membranes, with our data linking the autophagy defect upon SNX4 disruption to the mis-trafficking and/or retention of ATG9A in the Golgi region. Taken together, our findings show that the SNX4–SNX7 heterodimer coordinates ATG9A trafficking within the endocytic network to establish productive autophagosome assembly sites, thus extending knowledge of SNXs as positive regulators of autophagy. The Company of Biologists Ltd 2020-07-15 /pmc/articles/PMC7375690/ /pubmed/32513819 http://dx.doi.org/10.1242/jcs.246306 Text en © 2020. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/4.0This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Article Antón, Zuriñe Betin, Virginie M. S. Simonetti, Boris Traer, Colin J. Attar, Naomi Cullen, Peter J. Lane, Jon D. A heterodimeric SNX4–SNX7 SNX-BAR autophagy complex coordinates ATG9A trafficking for efficient autophagosome assembly |
title | A heterodimeric SNX4–SNX7 SNX-BAR autophagy complex coordinates ATG9A trafficking for efficient autophagosome assembly |
title_full | A heterodimeric SNX4–SNX7 SNX-BAR autophagy complex coordinates ATG9A trafficking for efficient autophagosome assembly |
title_fullStr | A heterodimeric SNX4–SNX7 SNX-BAR autophagy complex coordinates ATG9A trafficking for efficient autophagosome assembly |
title_full_unstemmed | A heterodimeric SNX4–SNX7 SNX-BAR autophagy complex coordinates ATG9A trafficking for efficient autophagosome assembly |
title_short | A heterodimeric SNX4–SNX7 SNX-BAR autophagy complex coordinates ATG9A trafficking for efficient autophagosome assembly |
title_sort | heterodimeric snx4–snx7 snx-bar autophagy complex coordinates atg9a trafficking for efficient autophagosome assembly |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375690/ https://www.ncbi.nlm.nih.gov/pubmed/32513819 http://dx.doi.org/10.1242/jcs.246306 |
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