Life Sciences Institute and Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Neuron. 2013 Jun 5;78(5):827-38. doi: 10.1016/j.neuron.2013.05.020.
Expression of the Down syndrome cell-adhesion molecule (Dscam) is increased in the brains of patients with several neurological disorders. Although Dscam is critically involved in many aspects of neuronal development, little is known about either the mechanism that regulates its expression or the functional consequences of dysregulated Dscam expression. Here, we show that Dscam expression levels serve as an instructive code for the size control of presynaptic arbor. Two convergent pathways, involving dual leucine zipper kinase (DLK) and fragile X mental retardation protein (FMRP), control Dscam expression through protein translation. Defects in this regulation of Dscam translation lead to exuberant presynaptic arbor growth in Drosophila somatosensory neurons. Our findings uncover a function of Dscam in presynaptic size control and provide insights into how dysregulated Dscam may contribute to the pathogenesis of neurological disorders.
唐氏综合征细胞黏附分子（Dscam）的表达在患有多种神经退行性疾病的患者大脑中增加。尽管 Dscam 在神经元发育的许多方面都有重要作用，但对于调节其表达的机制或失调的 Dscam 表达的功能后果知之甚少。在这里，我们表明 Dscam 的表达水平是作为对突触前树突生长大小的一个指令代码。两条会聚途径，涉及双亮氨酸拉链激酶（DLK）和脆性 X 智力低下蛋白（FMRP），通过蛋白质翻译来控制 Dscam 的表达。这种 Dscam 翻译调节的缺陷导致果蝇感觉神经元中突触前树突过度生长。我们的研究结果揭示了 Dscam 在突触前大小控制中的功能，并深入了解失调的 Dscam 如何导致神经退行性疾病的发病机制。
