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Tay桥和细胞外调节激酶活性是果蝇神经系统中运动神经元功能所必需的。

Tay bridge and extracellular-regulated kinase activity are required for motoneuron function in the Drosophila neural system.

作者信息

Molnar C, Estrada B, de Celis J F

机构信息

Centro de Biología Molecular "Severo Ochoa", CSIC and Universidad Autónoma de Madrid, Madrid, Spain.

Institute for Research in Biomedicine-Barcelona, Barcelona, Spain.

出版信息

Genes Brain Behav. 2018 Nov;17(8):e12470. doi: 10.1111/gbb.12470. Epub 2018 Apr 15.

Abstract

Extracellular regulated kinase (Erk) activity is required during neural development for the specification of cell fates in neuroblasts and neuronal lineages, and also regulates several aspects of the activity and survival of mature neurons. The activation of Erk is regulated at multiple levels by kinases and phosphatases that alter its phosphorylation state and by other proteins that regulate its subcellular localization. Here, we find that tay bridge (tay), a negative regulator of Erk in Drosophila imaginal discs, is required in the motoneurons to regulate the number and size of neuromuscular synapses in these cells. The expression of Tay is maximal in motoneurons with low levels of activated ERK, suggesting that Tay modulates the activity of Erk in these cells. We also found that loss of tay expression and increased Erk activity specifically in the motoneurons cause a reversible decrease in walking speed. Impaired motoneurons activity may be caused by alterations in the functionality and number of synaptic boutons developing at the neuromuscular junction in tay mutants.

摘要

在神经发育过程中,细胞外调节激酶(Erk)活性对于神经母细胞和神经元谱系中细胞命运的特化是必需的,并且还调节成熟神经元活性和存活的多个方面。Erk的激活在多个水平上受到激酶和磷酸酶的调节,这些激酶和磷酸酶会改变其磷酸化状态,还受到其他调节其亚细胞定位的蛋白质的调节。在这里,我们发现,果蝇成虫盘中Erk的负调节因子tay bridge(tay)在运动神经元中是调节这些细胞中神经肌肉突触数量和大小所必需的。Tay在活化ERK水平低的运动神经元中表达最高,这表明Tay调节这些细胞中Erk的活性。我们还发现,tay表达缺失以及特别是在运动神经元中Erk活性增加会导致行走速度可逆性降低。运动神经元活性受损可能是由于tay突变体神经肌肉接头处发育的突触小体的功能和数量改变所致。

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