Reference: Gao J, et al. (2018) Molecular mechanism to target the endosomal Mon1-Ccz1 GEF complex to the pre-autophagosomal structure. Elife 7

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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.

Reference Type
Journal Article | Research Support, Non-U.S. Gov't
Authors
Gao J, Langemeyer L, Kümmel D, Reggiori F, Ungermann C
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