Regulation of axon growth by the JIP1-AKT axis
Regulation of axon growth by the JIP1-AKT axis
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DOI：
10.1242/jcs.137208
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发表时间：
2014-01-01
影响因子：
4
通讯作者：
Whitmarsh, Alan J.
中科院分区：
文献类型：
--
作者：
Dajas-Bailador, Federico;Bantounas, Ioannis;Whitmarsh, Alan J.
发育中的神经元极化形成轴突和树突是建立神经元连接以实现正常大脑功能所必需的。蛋白激酶AKT和MAP激酶支架蛋白JNK相互作用蛋白-1(JIP1)是轴突形成的重要调节因子。在这里，我们报道了JIP1和AKT共同定位于皮质神经元的轴突生长锥体，并协同促进轴突生长。生长锥中AKT蛋白的丢失导致蛋白酶体对JIP1的降解，而JIP1的丢失也促进了AKT类似的命运。谷氨酸可以诱导生长锥中JIP1和AKT蛋白水平的降低，这与轴突生长减少是一致的，这可以通过稳定的JIP1突变体来拯救AKT蛋白水平。综上所述，我们的数据揭示了JIP1和AKT之间的协作关系，这种关系是轴突生长所必需的，可以通过神经元活动的变化来调节。
The polarisation of developing neurons to form axons and dendrites is required for the establishment of neuronal connections leading to proper brain function. The protein kinase AKT and the MAP kinase scaffold protein JNK-interacting protein-1 (JIP1) are important regulators of axon formation. Here we report that JIP1 and AKT colocalise in axonal growth cones of cortical neurons and collaborate to promote axon growth. The loss of AKT protein from the growth cone results in the degradation of JIP1 by the proteasome, and the loss of JIP1 promotes a similar fate for AKT. Reduced protein levels of both JIP1 and AKT in the growth cone can be induced by glutamate and this coincides with reduced axon growth, which can be rescued by a stabilized mutant of JIP1 that rescues AKT protein levels. Taken together, our data reveal a collaborative relationship between JIP1 and AKT that is required for axon growth and can be regulated by changes in neuronal activity.