Regulation of selective autophagy onset by a Ypt/Rab GTPase module
Regulation of selective autophagy onset by a Ypt/Rab GTPase module
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DOI：
10.1073/pnas.1121299109
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发表时间：
2012-05-01
影响因子：
11.1
通讯作者：
Segev, Nava
中科院分区：
文献类型：
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作者：
Lipatova, Zhanna;Belogortseva, Natalia;Segev, Nava
细胞内运输的关键调节因子，Ypt/Rab GTPases，受到特定的上游激活因子的刺激，当被激活时，招募特定的下游效应物来介导膜运输事件。酵母Ypt1及其人类功能同源物hRab1调节内质网（ER）到高尔基体的运输和自噬。然而，尚不清楚这些gtpase调节自噬的机制是否取决于它们在内质网到高尔基转运中的功能。在这里，我们确定了Atg11，自噬体前结构（PAS）组织者，作为Ypt1的下游效应者，并表明在正常生长条件下，Ypt1-Atg11相互作用是PAS组装所必需的。此外，我们发现Ypt1和Atg11与Ypt1激活子亚基Trs85共定位，并共同调节选择性自噬。最后，我们发现Ypt1和Trs85在含atg9的膜上相互作用，这是PAS的膜组分的来源。我们的研究结果共同定义了一个Ypt/Rab模块——包括一个激活剂、GTPase和效应剂——它协调选择性自噬的开始，这是一个对细胞稳态至关重要的过程。此外，由于Atg11不参与er -to-高尔基转运，我们在这里证明了Ypt/Rabs可以通过招募过程特异性效应物来调节两个独立的膜转运过程。
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 preautophagosomal 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 colocalize 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 the PAS. Together our results define a Ypt/Rab module-comprising an 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, we demonstrate here that Ypt/Rabs can regulate two independent membrane-transport processes by recruiting process-specific effectors.