The Ccz1-Mon1-Rab7 module and Rab5 control distinct steps of autophagy

Krisztina Hegedus, Szabolcs Takats, Attila Boda, Andras Jipa, Péter Nagy, Kata Varga, A. Kovács, G. Juhász

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

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 fnd 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.

Original languageEnglish
Pages (from-to)3132-3142
Number of pages11
JournalMolecular Biology of the Cell
Volume27
Issue number20
DOIs
Publication statusPublished - Oct 15 2016

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Autophagy
Lysosomes
Endosomes
Null Lymphocytes
Monomeric GTP-Binding Proteins
Guanosine
Starvation
Phosphatidylinositol 3-Kinases
Adipocytes
Drosophila
Autophagosomes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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The Ccz1-Mon1-Rab7 module and Rab5 control distinct steps of autophagy. / Hegedus, Krisztina; Takats, Szabolcs; Boda, Attila; Jipa, Andras; Nagy, Péter; Varga, Kata; Kovács, A.; Juhász, G.

In: Molecular Biology of the Cell, Vol. 27, No. 20, 15.10.2016, p. 3132-3142.

Research output: Contribution to journalArticle

Hegedus K, Takats S, Boda A, Jipa A, Nagy P, Varga K et al. The Ccz1-Mon1-Rab7 module and Rab5 control distinct steps of autophagy. Molecular Biology of the Cell. 2016 Oct 15;27(20):3132-3142. https://doi.org/10.1091/mbc.E16-03-0205
Hegedus, Krisztina ; Takats, Szabolcs ; Boda, Attila ; Jipa, Andras ; Nagy, Péter ; Varga, Kata ; Kovács, A. ; Juhász, G. / The Ccz1-Mon1-Rab7 module and Rab5 control distinct steps of autophagy. In: Molecular Biology of the Cell. 2016 ; Vol. 27, No. 20. pp. 3132-3142.
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