Regulation of Selective Autophagy Onset by a Ypt/Rab GTPase Module
Zhanna Lipatova
Natalia Belogortseva
Xiu Qi Zhang
Jane Kim
David Taussig
Nava Segev
10027/8412
https://indigo.uic.edu/articles/journal_contribution/Regulation_of_Selective_Autophagy_Onset_by_a_Ypt_Rab_GTPase_Module/10777841
The key regulators of intracellular trafficking, Ypt/Rab GTPases, are stimulated by specific upstream activators and, when activated, recruit specific downstream effectors to mediate membrane transport events. The yeast Ypt1 and its human functional homolog hRab1 regulate both endoplasmic reticulum (ER)-to-Golgi transport and autophagy. However, it is not clear whether the mechanism by which these GTPases
regulate autophagy depends on their well-documented function in ER-to-Golgi transport.
Here, we identify Atg11, the pre-autophagosomal structure (PAS) organizer, as a downstream effector of Ypt1 and show that the Ypt1-Atg11 interaction is required for
PAS assembly under normal growth conditions. Moreover, we show that Ypt1 and Atg11 co-localize with Trs85, a Ypt1 activator subunit, and together they regulate
selective autophagy. Finally, we show that Ypt1 and Trs85 interact on Atg9-containing
membranes, which serve as a source for the membrane component of PAS. Together
our results define the first Ypt/Rab module – comprising of activator, GTPase and
effector – that orchestrates the onset of selective autophagy, a process vital for cell
homeostasis. Furthermore, because Atg11 does not play a role in ER-to-Golgi transport,
this is the first demonstration that Ypt/Rabs can regulate two independent membrane
transport processes by recruiting process-specific effectors.
2012-07-24 00:00:00
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