Hippocampal neuronal polarity specified by spatially localized mPar3/mPar6 and PI 3-kinase activity
Hippocampal neuronal polarity specified by spatially localized mPar3/mPar6 and PI 3-kinase activity
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DOI：
10.1016/s0092-8674(02)01249-7
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发表时间：
2003-01-10
期刊：
影响因子：
64.5
通讯作者：
Jan, YN
中科院分区：
文献类型：
--
作者：
Shi, SH;Jan, LY;Jan, YN
神经元如何极化仍然是一个悬而未决的问题。在这里，我们报告说，选择未来的轴突之间的神经突起的培养海马神经元需要生长因子受体酪氨酸激酶，磷脂酰肌醇3-激酶（PI 3-激酶），以及非典型蛋白激酶C（aPKC）的活性。PI 3-激酶活性高度定位于第3阶段神经元的新指定轴突的尖端，对于mPar 3（C.线虫极性蛋白Par 3。不仅mPar 3而且mPar 6的极化分布对于轴突形成是重要的; mPar 6或mPar 3的异位表达，或仅mPar 3的N末端，留下没有指定轴突的神经元。因此，神经元的极性很可能是由mPar 3/mPar 6/aPKC复合物和PI 3-激酶信号通路控制的，这两种信号通路都在指定细胞极性中发挥进化上保守的作用。
How a neuron becomes polarized remains an outstanding question. Here, we report that selection of the future axon among neurites of a cultured hippocampal neuron requires the activity of growth factor receptor tyrosine kinase, phosphatidylinositol 3-kinase (PI 3-kinase), as well as atypical protein kinase C (aPKC). The PI 3-kinase activity, highly localized to the tip of the newly specified axon of stage 3 neurons, is essential for the proper subcellular localization of mPar3, the mammalian homolog of C. elegans polarity protein Par3. Polarized distribution of not only mPar3 but also mPar6 is important for axon formation; ectopic expression of mPar6 or mPar3, or just the N terminus of mPar3, leaves neurons with no axon specified. Thus, neuronal polarity is likely to be controlled by the mPar3/mPar6/aPKC complex and the PI 3-kinase signaling pathway, both serving evolutionarily conserved roles in specifying cell polarity.