J Neurosci:智力低下的神经发育分子调控机制

2014-02-24 遗传与发育生物学研究所 遗传与发育生物学研究所

人类的大脑由1000亿个神经元组成,神经元与神经元之间通过多达10000个神经突触相互连接形成一个庞大而复杂的神经网络,从而行使大脑的功能。因此,神经突触的发育和功能是神经生物学研究的核心内容。脂质的主要生理功能是储存能量、构成细胞膜组份以及调控膜信号转导。脂质在神经系统中富集,且对神经系统的发育和功能起着极其重要的作用。脂代谢异常导致多种神经精神疾病。例如参与脂肪酸在体内活化利用的第一步关键酶脂

人类的大脑由1000亿个神经元组成,神经元与神经元之间通过多达10000个神经突触相互连接形成一个庞大而复杂的神经网络,从而行使大脑的功能。因此,神经突触的发育和功能是神经生物学研究的核心内容。脂质的主要生理功能是储存能量、构成细胞膜组份以及调控膜信号转导。脂质在神经系统中富集,且对神经系统的发育和功能起着极其重要的作用。脂代谢异常导致多种神经精神疾病。例如参与脂肪酸在体内活化利用的第一步关键酶脂酰辅酶A合成酶(acyl-CoA synthetase long-chain family member 4, ACSL4)突变后特异性地导致智力低下而不影响其他生理功能。但是ACSL4及其所调控的脂质如何影响神经发育以及ACSL4突变后导致智力低下的发病机理目前还远不清楚。【原文下载】

ACSL4蛋白序列在进化上高度保守。中国科学院遗传与发育生物学研究所张永清组的研究发现果蝇ACSL4同源蛋白Acsl突变后导致三龄幼虫的神经肌肉突触过度生长。进一步的研究表明,Acsl突变体中的突触过度生长是由于促进突触生长的BMP(bone morphogenetic protein)信号通路活性异常升高所致。神经发育过程中的信号转导受到精细的调控。活化的BMP受体需要经过Rab11介导的内涵体循环进行灭活,从而抑制BMP通路的信号转导。该研究发现Acsl突变体中,循环内含体(recycling endosome)膜中的蛋白组份异常,与膜结合的Rab11降低,从而抑制内含体对BMP信号转导的负调控,最终导致神经突触过渡生长。这一研究揭示了ACSL4在神经突触发育过程中的功能及其分子调控机制,也为进一步深入研究脂质在神经系统中的功能以及相关神经精神疾病包括智力低下等的发病机制提供了理想的切入点。

上述研究结果以“特色报告”(featured article)的形式发表于最近一期的国际主流神经生物学杂志Journal of Neuroscience(19 February 2014, 34(8):2785-2796; doi:10.1523/JNEUROSCI.3547-13.2014)。实验室博士后刘志华和博士研究生黄琰为该论文的共同第一作者。这一工作得到了中国科学院脑先导专项和自然基金委重大国际合作项目的资助。

原始出处:

Zhihua Liu1,*, Yan Huang1,*, Wen Hu2, Sheng Huang1, Qifu Wang1, Junhai Han2, and Yong Q. Zhang1.dAcsl, the Drosophila Ortholog of Acyl-CoA Synthetase Long-Chain Family Member 3 and 4, Inhibits Synapse Growth by Attenuating Bone Morphogenetic Protein Signaling via Endocytic Recycling.The Journal of Neuroscience, 19 February 2014, 34(8): 2785-2796; doi: 10.1523/JNEUROSCI.3547-13.2014【原文下载】

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    2014-02-26 neurowu
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    2014-02-26 lsndxfj
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