The histone acetyltransferase Elp3 plays in active role in the control of synaptic bouton expansion and sleep in Drosophila.
The histone acetyltransferase Elp3 plays in active role in the control of synaptic bouton expansion and sleep in Drosophila.
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DOI：
10.1111/j.1471-4159.2010.06892.x
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发表时间：
2010-10
影响因子：
4.7
通讯作者：
Elefant F
中科院分区：
文献类型：
--
作者：
Singh N;Lorbeck MT;Zervos A;Zimmerman J;Elefant F
组蛋白乙酰转移酶Elp 3（Elongator Protein 3）是高度保守的Elongator复合物的催化亚基。Elp 3对于神经元细胞核和细胞质中Elongator的复杂功能是必不可少的，包括神经元运动基因的表观遗传控制和影响轴突分支和皮质神经元迁移的α-微管蛋白的乙酰化。因此，Elp 3的失调已经涉及特异性影响神经元功能的人类病症，包括家族性自主神经功能障碍（FD）（一种以感觉和自主神经系统变性为特征的疾病）和运动神经元变性病症肌萎缩性侧索硬化（ALS）。这些研究强调了ELP 3在神经发育和疾病中的重要性，以及需要进一步表征ELP 3在动物模型中体内神经发生所需的基于细胞核和细胞质的多种作用。在这份报告中，我们调查的行为和形态的后果，导致有针对性地减少Elp 3 HAT水平，特别是在发展中的果蝇神经系统。我们证明，神经发育过程中Elp 3的缺失会导致成年果蝇的过度活跃表型和睡眠丧失，突触终扣数量和轴突长度以及幼虫神经肌肉接头中的分支显着增加，以及某些已知基因的失调参与这些过程。我们的研究结果揭示了一个新的作用，Elp 3在调节突触终扣扩张神经发生过程中，可能与睡眠的要求。
The histone acetyltransferase Elp3 (Elongator Protein 3) is the catalytic subunit of the highly conserved Elongator complex. Elp3 is essential for the complex functions of Elongator in both the nucleus and cytoplasm of neurons, including the epigenetic control of neuronal motility genes and the acetylation of α-tubulin that affects axonal branching and cortical neuron migration. Accordingly, misregulation of Elp3 has been implicated in human disorders that specifically affect neuronal function, including Familial Dysautonomia (FD), a disease characterized by degeneration of the sensory and autonomic nervous system, and the motor neuron degenerative disorder amyotrophic lateral sclerosis (ALS). These studies underscore the importance of Elp3 in neurodevelopment and disease, and the need to further characterize the multiple nuclear and cytoplasmic based roles of ELP3 required for neurogenesis in animal models, in vivo. In this report, we investigate the behavioral and morphological consequences that result from targeted reduction of Elp3 HAT levels specifically in the developing Drosophila nervous system. We demonstrate that loss of Elp3 during neurodevelopment leads to a hyperactive phenotype and sleep loss in the adult flies, a significant expansion in synaptic bouton number and axonal length and branching in the larval neuromuscular junction as well as the misregulation of certain genes known to be involved in these processes. Our results uncover a novel role for Elp3 in the regulation of synaptic bouton expansion during neurogenesis that may be linked with a requirement for sleep.
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影响因子：
5.3
作者：
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通讯作者：
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DOI：
10.1073/pnas.202335999
发表时间：
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