Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Hegedűs, Krisztina, Takáts, Szabolcs, Boda, Attila, Jipa, András, Nagy, Péter, Varga, Kata, Kovács, Attila L., Juhász, Gábor
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2016
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
_version_ 1782460014222376960
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
work_keys_str_mv AT hegeduskrisztina theccz1mon1rab7moduleandrab5controldistinctstepsofautophagy
AT takatsszabolcs theccz1mon1rab7moduleandrab5controldistinctstepsofautophagy
AT bodaattila theccz1mon1rab7moduleandrab5controldistinctstepsofautophagy
AT jipaandras theccz1mon1rab7moduleandrab5controldistinctstepsofautophagy
AT nagypeter theccz1mon1rab7moduleandrab5controldistinctstepsofautophagy
AT vargakata theccz1mon1rab7moduleandrab5controldistinctstepsofautophagy
AT kovacsattilal theccz1mon1rab7moduleandrab5controldistinctstepsofautophagy
AT juhaszgabor theccz1mon1rab7moduleandrab5controldistinctstepsofautophagy
AT hegeduskrisztina ccz1mon1rab7moduleandrab5controldistinctstepsofautophagy
AT takatsszabolcs ccz1mon1rab7moduleandrab5controldistinctstepsofautophagy
AT bodaattila ccz1mon1rab7moduleandrab5controldistinctstepsofautophagy
AT jipaandras ccz1mon1rab7moduleandrab5controldistinctstepsofautophagy
AT nagypeter ccz1mon1rab7moduleandrab5controldistinctstepsofautophagy
AT vargakata ccz1mon1rab7moduleandrab5controldistinctstepsofautophagy
AT kovacsattilal ccz1mon1rab7moduleandrab5controldistinctstepsofautophagy
AT juhaszgabor ccz1mon1rab7moduleandrab5controldistinctstepsofautophagy