The JIP1 scaffold protein regulates axonal development in cortical neurons.
The JIP1 scaffold protein regulates axonal development in cortical neurons.
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DOI：
10.1016/j.cub.2008.01.025
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发表时间：
2008-02-12
期刊：
影响因子：
9.2
通讯作者：
Whitmarsh, Alan J.
中科院分区：
文献类型：
--
作者：
Dajas-Ballador, Federico;Jones, Emma V.;Whitmarsh, Alan J.
神经元极性的发展对于确定神经元连接和正确的脑功能至关重要。c-Jun N-末端激酶（JNK）相互作用蛋白-1（JIP 1）在神经元中高度表达，并且先前已被表征为JNK信号传导的调节剂。JIP 1已被证明在各种神经元模型中定位于神经突，但这种定位的功能意义尚未完全理解。JIP 1也是马达蛋白驱动蛋白-1的货物，其对于轴突运输是重要的。在这里，我们表明，初级皮质神经元极化之前，JIP 1专门定位于一个单一的轴突和轴突规范后，它积累在新兴的轴突。JIP 1是正常轴突发育所必需的，并依赖于其与驱动蛋白-1的结合以及通过新描述的与c-Abl酪氨酸激酶的相互作用来促进轴突生长。JIP 1与c-Abl结合并被c-Abl磷酸化，JIP 1上c-Abl磷酸化位点的突变废除了其促进轴突生长的能力。因此，JIP 1是轴突发育的重要调节因子，并且是控制轴突生长的c-Abl依赖性途径的关键靶标。
The development of neuronal polarity is essential for the determination of neuron connectivity and for correct brain function. The c-Jun N-terminal kinase (JNK)-interacting protein-1 (JIP1) is highly expressed in neurons and has previously been characterized as a regulator of JNK signaling. JIP1 has been shown to localize to neurites in various neuronal models, but the functional significance of this localization is not fully understood. JIP1 is also a cargo of the motor protein kinesin-1, which is important for axonal transport. Here we demonstrate that before primary cortical neurons become polarized, JIP1 specifically localizes to a single neurite and that after axonal specification, it accumulates in the emerging axon. JIP1 is necessary for normal axonal development and promotes axonal growth dependent upon its binding to kinesin-1 and via a newly described interaction with the c-Abl tyrosine kinase. JIP1 associates with and is phosphorylated by c-Abl, and the mutation of the c-Abl phosphorylation site on JIP1 abrogates its ability to promote axonal growth. JIP1 is therefore an important regulator of axonal development and is a key target of c-Abl-dependent pathways that control axonal growth.
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影响因子：
5.3
作者：
Dent, EW;Barnes, AM;Kalil, K
通讯作者：
Kalil, K
影响因子：
16.2
作者：
Jacobson, C;Schnapp, B;Banker, GA
通讯作者：
Banker, GA
影响因子：
9.2
作者：
Reed, Nathan A.;Cai, Dawen;Verhey, Kristen J.
通讯作者：
Verhey, Kristen J.
影响因子：
10.5
作者：
Whitmarsh, AJ;Kuan, CY;Davis, RJ
通讯作者：
Davis, RJ
DOI：
10.1083/jcb.200605099
发表时间：
2007-01-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Blasius TL;Cai D;Jih GT;Toret CP;Verhey KJ
通讯作者：
Verhey KJ