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The Ccz1-Mon1-Rab7 module and Rab5 control distinct steps of autophagy
The small GTPase Rab5 promotes recruitment of the Ccz1-Mon1 guanosine exchange complex to endosomes to activate Rab7, which facilitates endosome maturation and fusion with lysosomes. How these factors function during autophagy is incompletely understood. Here we show that autophagosomes accumulate d...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063620/ https://www.ncbi.nlm.nih.gov/pubmed/27559127 http://dx.doi.org/10.1091/mbc.E16-03-0205 |
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author | Hegedűs, Krisztina Takáts, Szabolcs Boda, Attila Jipa, András Nagy, Péter Varga, Kata Kovács, Attila L. Juhász, Gábor |
author_facet | Hegedűs, Krisztina Takáts, Szabolcs Boda, Attila Jipa, András Nagy, Péter Varga, Kata Kovács, Attila L. Juhász, Gábor |
author_sort | Hegedűs, Krisztina |
collection | PubMed |
description | The small GTPase Rab5 promotes recruitment of the Ccz1-Mon1 guanosine exchange complex to endosomes to activate Rab7, which facilitates endosome maturation and fusion with lysosomes. How these factors function during autophagy is incompletely understood. Here we show that autophagosomes accumulate due to impaired fusion with lysosomes upon loss of the Ccz1-Mon1-Rab7 module in starved Drosophila fat cells. In contrast, autophagosomes generated in Rab5-null mutant cells normally fuse with lysosomes during the starvation response. Consistent with that, Rab5 is dispensable for the Ccz1-Mon1–dependent recruitment of Rab7 to PI3P-positive autophagosomes, which are generated by the action of the Atg14-containing Vps34 PI3 kinase complex. Finally, we find that Rab5 is required for proper lysosomal function. Thus the Ccz1-Mon1-Rab7 module is required for autophagosome-lysosome fusion, whereas Rab5 loss interferes with a later step of autophagy: the breakdown of autophagic cargo within lysosomes. |
format | Online Article Text |
id | pubmed-5063620 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-50636202016-12-30 The Ccz1-Mon1-Rab7 module and Rab5 control distinct steps of autophagy Hegedűs, Krisztina Takáts, Szabolcs Boda, Attila Jipa, András Nagy, Péter Varga, Kata Kovács, Attila L. Juhász, Gábor Mol Biol Cell Articles The small GTPase Rab5 promotes recruitment of the Ccz1-Mon1 guanosine exchange complex to endosomes to activate Rab7, which facilitates endosome maturation and fusion with lysosomes. How these factors function during autophagy is incompletely understood. Here we show that autophagosomes accumulate due to impaired fusion with lysosomes upon loss of the Ccz1-Mon1-Rab7 module in starved Drosophila fat cells. In contrast, autophagosomes generated in Rab5-null mutant cells normally fuse with lysosomes during the starvation response. Consistent with that, Rab5 is dispensable for the Ccz1-Mon1–dependent recruitment of Rab7 to PI3P-positive autophagosomes, which are generated by the action of the Atg14-containing Vps34 PI3 kinase complex. Finally, we find that Rab5 is required for proper lysosomal function. Thus the Ccz1-Mon1-Rab7 module is required for autophagosome-lysosome fusion, whereas Rab5 loss interferes with a later step of autophagy: the breakdown of autophagic cargo within lysosomes. The American Society for Cell Biology 2016-10-15 /pmc/articles/PMC5063620/ /pubmed/27559127 http://dx.doi.org/10.1091/mbc.E16-03-0205 Text en © 2016 Hegedu˝s, Takáts, Boda, 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 Hegedűs, Krisztina Takáts, Szabolcs Boda, Attila Jipa, András Nagy, Péter Varga, Kata Kovács, Attila L. Juhász, Gábor The Ccz1-Mon1-Rab7 module and Rab5 control distinct steps of autophagy |
title | The Ccz1-Mon1-Rab7 module and Rab5 control distinct steps of autophagy |
title_full | The Ccz1-Mon1-Rab7 module and Rab5 control distinct steps of autophagy |
title_fullStr | The Ccz1-Mon1-Rab7 module and Rab5 control distinct steps of autophagy |
title_full_unstemmed | The Ccz1-Mon1-Rab7 module and Rab5 control distinct steps of autophagy |
title_short | The Ccz1-Mon1-Rab7 module and Rab5 control distinct steps of autophagy |
title_sort | ccz1-mon1-rab7 module and rab5 control distinct steps of autophagy |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063620/ https://www.ncbi.nlm.nih.gov/pubmed/27559127 http://dx.doi.org/10.1091/mbc.E16-03-0205 |
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