Molecular mechanism to target the endosomal Mon1-Ccz1 GEF complex to the pre-autophagosomal structure
Autor(en): | Gao, Jieqiong Langemeyer, Lars Kuemmel, Daniel Reggiori, Fulvio Ungermann, Christian |
Stichwörter: | ATG PROTEINS; BIOGENESIS; Biology; HOMOTYPIC FUSION; Life Sciences & Biomedicine - Other Topics; MEMBRANE-FUSION; NUCLEOTIDE EXCHANGE FACTOR; RAB7 GTPASE; SACCHAROMYCES-CEREVISIAE; SYNTAXIN HOMOLOG; UBIQUITIN-LIKE PROTEINS; VACUOLE | Erscheinungsdatum: | 2018 | Herausgeber: | ELIFE SCIENCES PUBLICATIONS LTD | Journal: | ELIFE | Volumen: | 7 | 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. |
ISSN: | 2050084X | DOI: | 10.7554/eLife.31145 |
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geprüft am 13.05.2024