Evidence for Developmentally Regulated Local Translation of Odorant Receptor mRNAs in the Axons of Olfactory Sensory Neurons
Evidence for Developmentally Regulated Local Translation of Odorant Receptor mRNAs in the Axons of Olfactory Sensory Neurons
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DOI：
10.1523/jneurosci.2443-09.2009
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发表时间：
2009-08-19
影响因子：
5.3
通讯作者：
Trembleau, Alain
中科院分区：
文献类型：
--
作者：
Dubacq, Caroline;Jamet, Sophie;Trembleau, Alain
气味受体mRNA在投射到嗅球中的嗅觉感觉神经元的轴突内转运。气味受体蛋白已被确定沿着这些轴突的远端部分，这提高了它们在轴突中局部合成的可能性。我们利用嗅觉粘膜（其中包含感觉神经元细胞体）和球（其中包含感觉轴突，但没有感觉神经元细胞体）之间的解剖分离，以解决这个问题，使用定量生化方法。结合一种方法，分离多核糖体相关的mRNA与非翻译的mRNA的逆转录定量PCR方法，我们证明了显着量的气味受体mRNA与多核糖体在成年小鼠球的感觉轴突。因此，我们提供了第一个证据，本地合成的气味受体蛋白在这些轴突。有趣的是，轴突中气味受体mRNA翻译的速率在未成熟轴突的比例较高的时期显著更高（即，在出生后第4天或在成年人化学损伤后再生时）。与此相反，嗅觉标记蛋白mRNA，这是有限的成熟轴突，翻译在一个低的和恒定的水平。总体而言，我们表明，轴突中的气味受体mRNA的翻译水平是发育调节的，并呈正相关的轴突生长到灯泡的阶段。鉴于气味受体在感觉投射的轴突布线中的既定功能，我们建议这种受调节的轴突翻译可能在肾小球阵列的发展和维持中发挥作用。
Odorant receptor mRNAs are transported within axons of olfactory sensory neurons that project into the olfactory bulb. Odorant receptor proteins have been identified along the distal part of these axons, which raises the possibility of their local synthesis in axons. We took advantage of the anatomical separation between the olfactory mucosa ( which contains the sensory neuron cell bodies) and the bulb ( which contains sensory axons but no sensory neuron cell bodies) to address this issue using a quantitative biochemical approach. Combining a method that separates polysome-associated mRNAs from untranslated mRNAs with a reverse transcription-quantitative PCR approach, we demonstrate that significant amounts of odorant receptor mRNAs are associated with polysomes in the sensory axons of the adult mouse bulb. We thus provide the first evidence for local synthesis of odorant receptor proteins in these axons. Interestingly, the rate of odorant receptor mRNA translation in axons is significantly greater during periods when the proportion of immature axons is higher (i.e., at postnatal day 4 or on regeneration after chemical lesion in adults). In contrast, the olfactory marker protein mRNA, which is restricted to mature axons, is translated at a low and constant level. Overall, we demonstrate that translation levels of odorant receptor mRNAs in axons are developmentally regulated, and positively correlated to the stage of axonal growth into the bulb. Given the established function of odorant receptors in the axonal wiring of sensory projections, we propose that this regulated axonal translation may play a role in the development and maintenance of the glomerular array.