A novel role for CAMKIIβ in the regulation of cortical neuron migration: implications for neurodevelopmental disorders
A novel role for CAMKIIβ in the regulation of cortical neuron migration: implications for neurodevelopmental disorders
复制标题
CAMKIIβ 在调节皮质神经元迁移中的新作用：对神经发育障碍的影响
作者：
O. Nicole;Donald M. Bell;T. Leste;Hélène Doat;F. Guillemot;E. Pacary
CaMKIIβ表达的扰动与多种神经精神疾病相关，突出了CaMKIIβ作为感兴趣的基因。然而，与CaMKIIα相反，CaMKIIβ在大脑中的特定功能仍然很少探索。在这里，我们揭示了一种新的功能，这种钙调激酶II亚型在体内神经元发育过程中。利用子宫内电穿孔技术，我们发现CaMK Ⅱ β是大脑皮质发育过程中投射神经元径向迁移的重要调节因子。CaMK II β的敲低导致新生锥体神经元的加速迁移，而CaMK II β的过表达抑制迁移，表明精确调节CaMK II β表达是正确的神经元迁移所必需的。更确切地说，CaMK Ⅱ β通过其肌动蛋白结合和成束活性控制中间区的多极-双极转换和皮质板的运动。此外，我们的数据表明，CaMKIIβ和cofilin活性之间的微调平衡是必要的，以确保皮质神经元的适当迁移。因此，我们的研究结果定义了CaMKIIβ的一种新的亚型特异性功能，表明CaMKIIβ在发育中的大脑中具有主要的生物学功能。
Perturbation of CaMKIIβ expression has been associated with multiple neuropsychiatric diseases, highlighting CaMKIIβ as a gene of interest. Yet, in contrast to CaMKIIα, the specific functions of CaMKIIβ in the brain remain poorly explored. Here, we reveal a novel function for this CaMKII isoform in vivo during neuronal development. By using in utero electroporation, we show that CaMKIIβ is an important regulator of radial migration of projection neurons during cerebral cortex development. Knockdown of CaMKIIβ causes accelerated migration of nascent pyramidal neurons, whereas overexpression of CaMKIIβ inhibits migration, demonstrating that precise regulation of CaMKIIβ expression is required for correct neuronal migration. More precisely, CaMKIIβ controls the multipolar–bipolar transition in the intermediate zone and locomotion in the cortical plate through its actin-binding and -bundling activities. In addition, our data indicate that a fine-tuned balance between CaMKIIβ and cofilin activities is necessary to ensure proper migration of cortical neurons. Thus, our findings define a novel isoform-specific function for CaMKIIβ, demonstrating that CaMKIIβ has a major biological function in the developing brain.
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DOI：
10.1146/annurev-cellbio-101512-122400
发表时间：
2013
影响因子：
11.3
作者：
Evsyukova I;Plestant C;Anton ES
通讯作者：
Anton ES
影响因子：
56.9
作者：
Shen, K;Meyer, T
通讯作者：
Meyer, T
影响因子：
56.9
作者：
MALINOW, R;SCHULMAN, H;TSIEN, RW
通讯作者：
TSIEN, RW
影响因子：
10.5
作者：
Oury, Franck;Yadav, Vijay K.;Karsenty, Gerard
通讯作者：
Karsenty, Gerard
影响因子：
56.9
作者：
Giese, KP;Fedorov, NB;Silva, AJ
通讯作者：
Silva, AJ