Plasma membrane to vacuole traffic induced by glucose starvation requires Gga2-dependent sorting at the trans-Golgi network.
Plasma membrane to vacuole traffic induced by glucose starvation requires Gga2-dependent sorting at the trans-Golgi network.
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DOI：
10.1111/boc.202000058
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发表时间：
2020-11
影响因子：
2.7
通讯作者：
Duncan MC
中科院分区：
文献类型：
--
作者：
Buelto D;Hung CW;Aoh QL;Lahiri S;Duncan MC
在酿酒酵母中，急性葡萄糖饥饿会诱导快速内吞作用，随后许多质膜蛋白发生液泡降解。这个过程对于细胞活力至关重要，但控制它的调节机制仍然知之甚少。在正常生长条件下，内吞货物的主要调节决定发生在跨高尔基体网络（TGN），其中蛋白质可以循环回到质膜，或者可以被 TGN 定位的网格蛋白接头识别，将它们引导至液泡。然而，葡萄糖饥饿会减少回收并改变 TGN 定位网格蛋白接头的定位和翻译后修饰。这提出了一种可能性，即在葡萄糖饥饿期间，内吞蛋白通过绕过 TGN 或不需要 TGN 定位的网格蛋白接头的新机制被路由至液泡。在这里，我们研究了葡萄糖饥饿期间 TGN 定位的网格蛋白接头在几种氨基酸通透酶（包括 Can1）运输中的作用。我们发现，在饥饿和正常条件下，Can1 在内吞作用后都会通过 TGN。 Can1 和其他氨基酸通透酶需要 TGN 定位的网格蛋白接头才能最大程度地递送至液泡。此外，这些通透酶被主动分选至液泡，因为 TGN 处的异位强制去泛素化导致饥饿细胞中 Tat1 通透酶的回收。最后，我们报告 Mup1 通透酶需要网格蛋白接头 Gga2 来进行液泡递送。相比之下，网格蛋白接头蛋白复合物 AP-1 发挥次要作用，可能在保留 TGN 中的通透酶方面发挥作用，但对于液泡递送来说它是可有可无的。这项工作阐明了酵母响应急性葡萄糖饥饿所需的一种膜运输途径。它还揭示了 TGN 局部网格蛋白接头在此过程中的功能。我们的结果表明，在葡萄糖饥饿的细胞中，在 GN 处进行液泡蛋白分选所需要的机制与在存在葡萄糖的情况下所需要的机制相同。此外，我们的研究结果进一步支持了以下模型：TGN 是许多内吞蛋白的转运点，并且 Gga2 和 AP-1 在 TGN 的不同途径中发挥作用。
In the yeast Saccharomyces cerevisiae, acute glucose starvation induces rapid endocytosis followed by vacuolar degradation of many plasma membrane proteins. This process is essential for cell viability, but the regulatory mechanisms that control it remain poorly understood. Under normal growth conditions, a major regulatory decision for endocytic cargo occurs at the trans‐Golgi network (TGN) where proteins can recycle back to the plasma membrane or can be recognized by TGN‐localised clathrin adaptors that direct them towards the vacuole. However, glucose starvation reduces recycling and alters the localization and post‐translational modification of TGN‐localised clathrin adaptors. This raises the possibility that during glucose starvation endocytosed proteins are routed to the vacuole by a novel mechanism that bypasses the TGN or does not require TGN‐localised clathrin adaptors. Here, we investigate the role of TGN‐localised clathrin adaptors in the traffic of several amino acid permeases, including Can1, during glucose starvation. We find that Can1 transits through the TGN after endocytosis in both starved and normal conditions. Can1 and other amino acid permeases require TGN‐localised clathrin adaptors for maximal delivery to the vacuole. Furthermore, these permeases are actively sorted to the vacuole, because ectopically forced de‐ubiquitination at the TGN results in the recycling of the Tat1 permease in starved cells. Finally, we report that the Mup1 permease requires the clathrin adaptor Gga2 for vacuolar delivery. In contrast, the clathrin adaptor protein complex AP‐1 plays a minor role, potentially in retaining permeases in the TGN, but it is otherwise dispensable for vacuolar delivery. This work elucidates one membrane trafficking pathway needed for yeast to respond to acute glucose starvation. It also reveals the functions of TGN localised clathrin adaptors in this process. Our results indicate that the same machinery is needed for vacuolar protein sorting at the GN in glucose starved cells as is needed in the presence of glucose. In addition, our findings provide further support for the model that the TGN is a transit point for many endocytosed proteins, and that Gga2 and AP‐1 function in distinct pathways at the TGN.
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影响因子：
3.3
作者：
Appadurai, Daniel;Gay, Lincoln;Babst, Markus
通讯作者：
Babst, Markus
影响因子：
4.5
作者：
Castillon, Guillaume A.;Burriat-Couleru, Patricia;Watanabe, Reika
通讯作者：
Watanabe, Reika
影响因子：
3.3
作者：
Gaynor, EC;Chen, CY;Graham, TR
通讯作者：
Graham, TR
影响因子：
3.3
作者：
Aoh QL;Hung CW;Duncan MC
通讯作者：
Duncan MC
影响因子：
3.3
作者：
Costaguta, G;Stefan, CJ;Payne, GS
通讯作者：
Payne, GS