Energy metabolism regulates clathrin adaptors at the trans-Golgi network and endosomes.
Energy metabolism regulates clathrin adaptors at the trans-Golgi network and endosomes.
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DOI：
10.1091/mbc.e12-10-0750
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发表时间：
2013-03
影响因子：
3.3
通讯作者：
Duncan MC
中科院分区：
文献类型：
--
作者：
Aoh QL;Hung CW;Duncan MC
内体网格蛋白衔接子的定位通过未知的机制由葡萄糖可用性调节。在完整和透化细胞中的研究表明，网格蛋白衔接子定位精确地调节细胞ATP浓度。这些数据为膜运输如何与总体增殖速率相协调提供了证据。葡萄糖是酿酒酵母中细胞行为的主要调节剂。它既是一种代谢底物，也是细胞内信号级联的有效调节剂。葡萄糖饥饿诱导网格蛋白衔接子在高尔基体网络和内体的短暂离域和部分再定位。虽然这些定位反应是已知的依赖于蛋白激酶A（PKA）信号通路，这种调节的分子机制是未知的。在这里，我们证明PKA和AMP调节激酶通过能量代谢的变化调节接头定位。我们发现，遗传和化学操纵细胞内ATP水平引起相应的变化，适配器定位。在透化细胞中，外源性ATP足以诱导接头定位。此外，我们揭示了不同的能量依赖的步骤，在适配器本地化：一个步骤，需要ADP-核糖基化因子ARF，ATP依赖的步骤，需要磷脂酰肌醇-4激酶Pik 1，和第三ATP依赖的步骤，我们提供的证据，但其机制是未知的。我们建议，这些能量依赖性机制精确地同步膜交通与整体增殖率，并有助于在急性葡萄糖饥饿的能量守恒的一个重要方面。
Localization of endosomal clathrin adaptors is regulated by glucose availability via an unknown mechanism. Studies in intact and permeabilized cells show that clathrin adaptor localization is precisely tuned by cellular ATP concentration. These data provide evidence for how membrane traffic is coordinated with overall proliferation rates. Glucose is a master regulator of cell behavior in the yeast Saccharomyces cerevisiae. It acts as both a metabolic substrate and a potent regulator of intracellular signaling cascades. Glucose starvation induces the transient delocalization and then partial relocalization of clathrin adaptors at the trans-Golgi network and endosomes. Although these localization responses are known to depend on the protein kinase A (PKA) signaling pathway, the molecular mechanism of this regulation is unknown. Here we demonstrate that PKA and the AMP-regulated kinase regulate adaptor localization through changes in energy metabolism. We show that genetic and chemical manipulation of intracellular ATP levels cause corresponding changes in adaptor localization. In permeabilized cells, exogenous ATP is sufficient to induce adaptor localization. Furthermore, we reveal distinct energy-dependent steps in adaptor localization: a step that requires the ADP-ribosylation factor ARF, an ATP-dependent step that requires the phosphatidyl-inositol-4 kinase Pik1, and third ATP-dependent step for which we provide evidence but for which the mechanism is unknown. We propose that these energy-dependent mechanisms precisely synchronize membrane traffic with overall proliferation rates and contribute a crucial aspect of energy conservation during acute glucose starvation.