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

Hegedűs, Krisztina and Takáts, Szabolcs and Boda, Attila and Jipa, András and Nagy, Péter and Varga, Kata and Juhász, Gábor and Kovács, Attila L. (2016) The Ccz1-Mon1-Rab7 module and Rab5 control distinct steps of autophagy. MOLECULAR BIOLOGY OF THE CELL, 27 (20). pp. 3132-3142. ISSN 1059-1524

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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.

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