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首页> 外文期刊>Cell motility and the cytoskeleton >Melatonin induction of filamentous structures in non-neuronal cells that is dependent on expression of the human mt1 melatonin receptor.
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Melatonin induction of filamentous structures in non-neuronal cells that is dependent on expression of the human mt1 melatonin receptor.

机译：褪黑激素诱导非神经元细胞中的丝状结构，这取决于人类mt1褪黑激素受体的表达。

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摘要

Melatonin has gained recent popularity as a treatment for insomnia and other sleep disorders; however, its cellular effects are unknown. We report the effects of melatonin on the cellular morphology of Chinese hamster ovary (CHO) cells transformed to express the human melatonin receptors, mt1 and MT2. Our results show that melatonin exerts a strong influence on cellular shape and cytoskeletal organization in a receptor-dependent and possibly subtype-selective manner. The cell shape change that we see after a 5-h treatment of these non-neuronal cells with a pharmacological concentration of melatonin consists of the formation of long filamentous outgrowths that are reminiscent of the neurite processes produced by differentiating nerve cells. This morphological change occurs exclusively in cells expressing the mt1 receptor. We find that the microtubule and microfilament organization within these outgrowths is similar to that of neurites. Microtubules are required for the shape change to occur as Colcemid added in combination with melatonin completely blocks outgrowth formation. We demonstrate that the number of cells showing the altered cell shape is dependent on melatonin concentration, constant exposure to melatonin and that outgrowth frequencies increase when protein kinase A (PKA) is inhibited. Concomitant melatonin-dependent increases in MEK 1/2 and ERK 1/2 phosphorylation are noted in mt1-CHO cells only. The production of filamentous outgrowths is dependent on the translation of new protein but not the transcription of new mRNA. Outgrowth number is not controlled by centrosomes but is instead controlled by the polymerization state of the actin cytoskeleton. The results of this work show that the organization of the cytoskeleton is affected by processes specifically mediated or regulated by the mt1 receptor and may represent a novel alternative mechanism for the stimulation of process formation. Copyright 2000 Wiley-Liss, Inc.
机译：褪黑素作为失眠症和其他睡眠障碍的治疗方法最近已广受欢迎。然而，其细胞作用尚不清楚。我们报告褪黑激素对中国仓鼠卵巢（CHO）细胞转化为表达人类褪黑激素受体mt1和​​MT2的细胞形态的影响。我们的研究结果表明，褪黑激素以受体依赖性和亚型选择性的方式对细胞的形状和细胞骨架组织产生强大的影响。在用褪黑激素的药理学浓度对这些非神经元细胞进行5小时处理后，我们看到细胞的形状变化包括长丝状长出，这使人联想到分化神经细胞所产生的神经突过程。这种形态变化仅发生在表达mt1受体的细胞中。我们发现这些产物中的微管和微丝组织与神经突相似。当将Colcemid与褪黑素组合添加时，微管是必要的，以使形状发生变化，从而完全阻止了突起的形成。我们证明，显示改变细胞形状的细胞数量取决于褪黑激素浓度，对褪黑激素的持续暴露，并且当蛋白激酶A（PKA）被抑制时，生长频率增加。仅在mt1-CHO细胞中发现了褪黑激素依赖性的MEK 1/2和ERK 1/2磷酸化增加。丝状产物的产生取决于新蛋白的翻译，而不取决于新mRNA的转录。增生数目不受中心体控制，而是受肌动蛋白细胞骨架的聚合状态控制。这项工作的结果表明，细胞骨架的组织受mt1受体特异介导或调节的过程的影响，并且可能代表了刺激过程形成的新型替代机制。版权所有2000 Wiley-Liss，Inc.

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