在人类新皮层发育过程中,人类特异性和猿类特异性代谢调节者的功能协同作用
Lei Xing1,2, Vasiliki Gkini3, Anni I Nieminen4
1Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany. lei.xing@umanitoba.ca.
Nature communications
|April 24, 2024
概括
人类新皮层扩张与新陈代谢有关. 人类特异性的ARHGAP11B基因和猿类特异性的GLUD2蛋白一起工作,促进基底辐射质细胞,增加大脑大小.
科学领域:
- 进化生物学是进化的生物学.
- 神经科学是一个神经科学.
- 代谢途径 代谢途径
背景情况:
- 代谢被越来越多地认为是人类新皮层进化扩张的关键因素.
- 人类特异性基因ARHGAP11B在新皮层发育中发挥作用,通过增加基本辐射质细胞,这对大脑生长至关重要.
- ARHGAP11B刺激线粒体内的谷氨酸溶解,将谷氨酸转化为谷氨酸,然后转化为α-谷氨酸.
研究的目的:
- 研究ARHGAP11B和GLUD2在调节基底辐射质丰度中的相互作用.
- 阐明由这些基因驱动的新皮质扩张背后的代谢机制.
主要方法:
- 使用双转基因模型,在基底辐射质 (bRG) 中表达ARHGAP11B和GLUD2.
- 在这些工程细胞中分析了代谢变化,包括代谢物生产和途径活性.
- 检查了对基底辐射质扩散和丰富性的影响.
主要成果:
- 特定于猿类的蛋白质GLUD2增强了ARHGAP11B增加基底辐射质细胞的能力.
- ARHGAP11B和GLUD2的共同表达导致通过α-甲酸盐和TCA循环从谷氨酸中产生高酸盐的产量.
- 这种新陈代谢增强支持增加的祖细胞增殖.
结论:
- 在人类进化过程中,人类特异性的ARHGAP11B基因利用了先前存在的猿类特异性GLUD2基因来增加新皮质的大小.
- 协调的新陈代谢变化,包括谷氨酸溶解和TCA循环,对于增加原始细胞数量和大脑扩张至关重要.
- 这项研究强调了基因进化和代谢调节在塑造人类大脑发育中的相互作用.
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