A CaMKII-NeuroD signaling pathway specifies dendritic morphogenesis
A CaMKII-NeuroD signaling pathway specifies dendritic morphogenesis
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DOI：
10.1016/s0896-6273(03)00841-9
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发表时间：
2004-01-22
期刊：
影响因子：
16.2
通讯作者：
Bonni, A
中科院分区：
文献类型：
--
作者：
Gaudillière, B;Konishi, Y;Bonni, A
树突的发育对于神经元极性和连接的建立至关重要，但树突形态发生的机制却知之甚少。我们发现，在包括器官型小脑切片在内的初级颗粒神经元中，转录因子NeuroD的遗传敲低严重损害了树突的产生和维持，同时保留了轴突的发育。我们还发现，NeuroD介导的神经元活性依赖性树突状细胞。活性诱导的蛋白激酶CaMKII在不同的位点催化NeuroD的磷酸化，包括原代神经元中Ser 336的内源性NeuroD，从而刺激树突状细胞的生长。这些发现揭示了NeuroD在颗粒神经元树突形态发生中的重要功能。我们的研究还将CaMKII-NeuroD信号通路定义为活性调节树突状细胞生长的一种新机制，可能在发育和成熟的大脑中发挥重要作用。
The elaboration of dendrites is fundamental to the establishment of neuronal polarity and connectivity, but the mechanisms that underlie dendritic morphogenesis are poorly understood. We found that the genetic knockdown of the transcription factor NeuroD in primary granule neurons including in organotypic cerebellar slices profoundly impaired the generation and maintenance of dendrites while sparing the development of axons. We also found that NeuroD mediated neuronal activity-dependent dendritogenesis. The activity-induced protein kinase CaMKII catalyzed the phosphorylation of NeuroD at distinct sites, including endogenous NeuroD at Ser336 in primary neurons, and thereby stimulated dendritic growth. These findings uncover an essential function for NeuroD in granule neuron dendritic morphogenesis. Our study also defines the CaMKII-NeuroD signaling pathway as a novel mechanism underlying activity-regulated dendritic growth that may play important roles in the developing and mature brain.