Molecular mechanism to target the endosomal Mon1-Ccz1 GEF complex to the pre-autophagosomal structure

Gao J, Langemeyer L, Kümmel D, Reggiori F, Ungermann C

Research article (journal) | Peer reviewed

Abstract

During autophagy, a newly formed double membrane surrounds its cargo to generate the so-called autophagosome, which then fuses with a lysosome after closure. Previous work implicated that endosomal Rab7/Ypt7 associates to autophagosomes prior to their fusion with lysosomes. Here, we unravel how the Mon1-Ccz1 guanosine exchange factor (GEF) acting upstream of Ypt7 is specifically recruited to the pre-autophagosomal structure under starvation conditions. We find that Mon1-Ccz1 directly binds to Atg8, the yeast homolog of the members of the mammalian LC3 protein family. This requires at least one LIR motif in the Ccz1 C-terminus, which is essential for autophagy but not for endosomal transport. In agreement, only wild-type, but not LIR-mutated Mon1-Ccz1 promotes Atg8-dependent activation of Ypt7. Our data reveal how GEF targeting can specify the fate of a newly formed organelle and provide new insights into the regulation of autophagosome-lysosome fusion.

Details about the publication

JournaleLife
Volume7
StatusPublished
Release year2018
Language in which the publication is writtenEnglish
DOI10.7554/eLife.31145
KeywordsAutophagosomes/metabolism; Autophagy-Related Protein 8 Family/metabolism; Guanine Nucleotide Exchange Factors/metabolism; Protein Multimerization; Protein Transport; rab GTP-Binding Proteins/metabolism; Saccharomyces cerevisiae Proteins/metabolism; Saccharomyces cerevisiae/enzymology/metabolism; Vesicular Transport Proteins/metabolism

Authors from the University of Münster

Kümmel, Daniel
Professorship for biochemistry and structural biology (Prof. Kümmel)