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LAMP-2 is required for incorporating syntaxin-17 into autophagosomes and for their fusion with lysosomes
Autophagy is an evolutionarily conserved process used for removing surplus and damaged proteins and organelles from the cytoplasm. The unwanted material is incorporated into autophagosomes that eventually fuse with lysosomes, leading to the degradation of their cargo. The fusion event is mediated by...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists Ltd
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5087675/ https://www.ncbi.nlm.nih.gov/pubmed/27628032 http://dx.doi.org/10.1242/bio.018648 |
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author | Hubert, Virginie Peschel, Andrea Langer, Brigitte Gröger, Marion Rees, Andrew Kain, Renate |
author_facet | Hubert, Virginie Peschel, Andrea Langer, Brigitte Gröger, Marion Rees, Andrew Kain, Renate |
author_sort | Hubert, Virginie |
collection | PubMed |
description | Autophagy is an evolutionarily conserved process used for removing surplus and damaged proteins and organelles from the cytoplasm. The unwanted material is incorporated into autophagosomes that eventually fuse with lysosomes, leading to the degradation of their cargo. The fusion event is mediated by the interaction between the Qa-SNARE syntaxin-17 (STX17) on autophagosomes and the R-SNARE VAMP8 on lysosomes. Cells deficient in lysosome membrane-associated protein-2 (LAMP-2) have increased numbers of autophagosomes but the underlying mechanism is poorly understood. By transfecting LAMP-2-deficient and LAMP-1/2-double-deficient mouse embryonic fibroblasts (MEFs) with a tandem fluorescent-tagged LC3 we observed a failure of fusion between the autophagosomes and the lysosomes that could be rescued by complementation with LAMP-2A. Although we observed no change in expression and localization of VAMP8, its interacting partner STX17 was absent from autophagosomes of LAMP-2-deficient cells. Thus, LAMP-2 is essential for STX17 expression by the autophagosomes and this absence is sufficient to explain their failure to fuse with lysosomes. The results have clear implications for situations associated with a reduction of LAMP-2 expression. |
format | Online Article Text |
id | pubmed-5087675 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The Company of Biologists Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-50876752016-10-31 LAMP-2 is required for incorporating syntaxin-17 into autophagosomes and for their fusion with lysosomes Hubert, Virginie Peschel, Andrea Langer, Brigitte Gröger, Marion Rees, Andrew Kain, Renate Biol Open Research Article Autophagy is an evolutionarily conserved process used for removing surplus and damaged proteins and organelles from the cytoplasm. The unwanted material is incorporated into autophagosomes that eventually fuse with lysosomes, leading to the degradation of their cargo. The fusion event is mediated by the interaction between the Qa-SNARE syntaxin-17 (STX17) on autophagosomes and the R-SNARE VAMP8 on lysosomes. Cells deficient in lysosome membrane-associated protein-2 (LAMP-2) have increased numbers of autophagosomes but the underlying mechanism is poorly understood. By transfecting LAMP-2-deficient and LAMP-1/2-double-deficient mouse embryonic fibroblasts (MEFs) with a tandem fluorescent-tagged LC3 we observed a failure of fusion between the autophagosomes and the lysosomes that could be rescued by complementation with LAMP-2A. Although we observed no change in expression and localization of VAMP8, its interacting partner STX17 was absent from autophagosomes of LAMP-2-deficient cells. Thus, LAMP-2 is essential for STX17 expression by the autophagosomes and this absence is sufficient to explain their failure to fuse with lysosomes. The results have clear implications for situations associated with a reduction of LAMP-2 expression. The Company of Biologists Ltd 2016-09-14 /pmc/articles/PMC5087675/ /pubmed/27628032 http://dx.doi.org/10.1242/bio.018648 Text en © 2016. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Article Hubert, Virginie Peschel, Andrea Langer, Brigitte Gröger, Marion Rees, Andrew Kain, Renate LAMP-2 is required for incorporating syntaxin-17 into autophagosomes and for their fusion with lysosomes |
title | LAMP-2 is required for incorporating syntaxin-17 into autophagosomes and for their fusion with lysosomes |
title_full | LAMP-2 is required for incorporating syntaxin-17 into autophagosomes and for their fusion with lysosomes |
title_fullStr | LAMP-2 is required for incorporating syntaxin-17 into autophagosomes and for their fusion with lysosomes |
title_full_unstemmed | LAMP-2 is required for incorporating syntaxin-17 into autophagosomes and for their fusion with lysosomes |
title_short | LAMP-2 is required for incorporating syntaxin-17 into autophagosomes and for their fusion with lysosomes |
title_sort | lamp-2 is required for incorporating syntaxin-17 into autophagosomes and for their fusion with lysosomes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5087675/ https://www.ncbi.nlm.nih.gov/pubmed/27628032 http://dx.doi.org/10.1242/bio.018648 |
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