title: The Ccz1-Mon1-Rab7 module and Rab5 control distinct steps of autophagy.
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 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.
authors: Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest H-1117, Hungary.
authors: Krisztina
authors: K
authors: Hegedűs
authors: Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest H-1117, Hungary sz.takats@ttk.elte.hu szmrt@elte.hu.
authors: Szabolcs
authors: S
authors: Takáts
authors: Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest H-1117, Hungary.
authors: Attila
authors: A
authors: Boda
authors: Institute of Genetics, Biological Research Centre, Szeged H-6726, Hungary.
authors: András
authors: A
authors: Jipa
authors: Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest H-1117, Hungary.
authors: Péter
authors: P
authors: Nagy
authors: Institute of Genetics, Biological Research Centre, Szeged H-6726, Hungary.
authors: Kata
authors: K
authors: Varga
authors: Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest H-1117, Hungary.
authors: Attila L
authors: AL
authors: Kovács
authors: Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest H-1117, Hungary Institute of Genetics, Biological Research Centre, Szeged H-6726, Hungary sz.takats@ttk.elte.hu szmrt@elte.hu.
authors: Gábor
authors: G
authors: Juhász
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D004330:Drosophila / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D010588:Phagosomes / Q000378:metabolism; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D014617:Vacuoles / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism; D000090802:rab7 GTP-Binding Proteins
chemical_list: C441960:Ccz1 protein, S cerevisiae; D029721:Drosophila Proteins; D020662:Guanine Nucleotide Exchange Factors; C470635:Mon1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins; D000090802:rab7 GTP-Binding Proteins; D020691:rab GTP-Binding Proteins; D020696:rab5 GTP-Binding Proteins