GLUT4 Mobilization Supports Energetic Demands of Active Synapses.
GLUT4 Mobilization Supports Energetic Demands of Active Synapses.
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GLUT4 动员支持活跃突触的能量需求。
DOI：
10.1016/j.neuron.2016.12.020
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发表时间：
2017-02-08
期刊：
影响因子：
16.2
通讯作者：
Ryan TA
中科院分区：
文献类型：
--
作者：
Ashrafi G;Wu Z;Farrell RJ;Ryan TA
大脑对适当的燃料可用性高度敏感，如缺血发作和急性严重低血糖期间神经元功能的快速下降所证明的。我们以前表明，持续的突触前功能需要活动驱动的糖酵解。在这里，我们提供了强有力的证据表明，在动作电位（AP）放电，神经末梢依赖于葡萄糖转运蛋白Glut4作为糖酵解调节系统，以满足活动驱动的能量需求增加。突触处的活性触发Glut4插入轴突质膜，这是由代谢传感器AMP激酶的激活驱动的。此外，我们表明，Glut4的基因消融导致突触囊泡循环在持续AP放电，类似于急性葡萄糖剥夺期间观察到的逮捕。对这种生化调节系统的依赖“锻炼”突触让人想起发生在锻炼肌肉以维持细胞功能，并确定神经末梢作为适当代谢控制的关键部位。
The brain is highly sensitive to proper fuel availability as evidenced by the rapid decline in neuronal function during ischemic attacks and acute severe hypoglycemia. We previously showed that sustained presynaptic function requires activity-driven glycolysis. Here, we provide strong evidence that during action potential (AP) firing, nerve terminals rely on the glucose transporter Glut4 as a glycolytic regulatory system to meet the activity-driven increase in energy demands. Activity at synapses triggers insertion of Glut4 into the axonal plasma membrane driven by activation of the metabolic sensor AMP kinase. Furthermore, we show that genetic ablation of Glut4 leads to an arrest of synaptic vesicle recycling during sustained AP firing, similar to what is observed during acute glucose deprivation. The reliance on this biochemical regulatory system for “exercising” synapses is reminiscent of that occurring in exercising muscle to sustain cellular function, and identifies nerve terminals as critical sites of proper metabolic control.