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

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Titel: Molecular mechanism to target the endosomal Mon1-Ccz1 GEF complex to the pre-autophagosomal structure
Autor(en): Jieqiong, Gao
Langemeyer, Lars
Kümmel, Daniel
Reggiori, Fulvio
Ungermann, Christian
ORCID des Autors:
Zusammenfassung: 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.
Bibliografische Angaben: eLife 2018;7:e31145
Schlagworte: endosomal Mon1-Ccz1 GEF complex; pre-autophagosomal
Erscheinungsdatum: 15-Feb-2018
Lizenzbezeichnung: Attribution 4.0 International
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