中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (12): 2397-2398.doi: 10.4103/1673-5374.313035

• 观点:神经损伤修复保护与再生 • 上一篇    下一篇

探索控制小神经胶质细胞异质性和过渡的基因

  

  • 出版日期:2021-12-15 发布日期:2021-05-14

Exploring genes that control microglial heterogeneity and transition

Tomomi Okajima, Fuminori Tsuruta*   

  1. Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan (Okajima T);Master’s and Doctoral Programs in Biology, Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan (Tsuruta F) ;Master’s and Doctoral Program in Neuroscience, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan (Tsuruta F);PhD Program in Human Biology, School of Integrative and Global Majors, University of Tsukuba, Tsukuba, Ibaraki, Japan (Tsuruta F);PhD Program in Humanics, School of Integrative and Global Majors, University of Tsukuba, Tsukuba, Ibaraki, Japan (Tsuruta F)
  • Online:2021-12-15 Published:2021-05-14
  • Contact: Fuminori Tsuruta, PhD, tsuruta.fuminori.fn@u.tsukuba.ac.jp.
  • Supported by:
    We apologize to the many authors whose papers could not be cited due to space limitations. I would like to thank the members of our laboratory for the helpful discussion.

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摘要：

Neural Regen Res：脂肪非典型钙粘蛋白家族蛋白3（FAT3）与小胶质细胞转变和功能的相关性

   小胶质细胞是中枢神经系统的常驻免疫细胞，通过监测其微环境有助于维持大脑内稳态。最近的研究报道，小胶质细胞可调节出生后神经回路的形成。小胶质细胞的功能转变被认为与它们随时间的形态变化有关。虽然小胶质细胞的形态被发现受到特定基因表达的调控，但小胶质细胞形态变化的机制尚未完全阐明。最近研究报道了脂肪非典型钙粘蛋白家族蛋白3（FAT3）是一种稳定次黄嘌呤调节的小胶质细胞过程的新因子。由于FAT3表达的时间与出生后小胶质细胞形态变化的时间一致，因此FAT3调控小胶质细胞的转变是合理的。

    来自日本筑波大学的Fuminori Tsuruta团队发现高浓度次黄嘌呤是合成肌苷一磷酸的中间产物，它能诱导小胶质细胞FAT3的生成。次黄嘌呤诱导的FAT3表达可显著抑制小胶质细胞突起的收缩，从而增加延长的小胶质细胞株BV2的数量。虽然次黄嘌呤如何促进FAT3表达的机制至今仍不清楚，但这一观察结果表明，FAT3的功能之一是稳定小胶质细胞中的肌动蛋白细胞骨架。有趣的是，小胶质细胞Fat3在出生后2-3周左右表达。这个时间与出生后阶段的小胶质细胞转变和突触形成是一致的。大脑中的一些FAT3蛋白定位在突触部位。FAT3通过与几种支架蛋白的相互作用而锚定在突触中是合理的。事实上，FAT3具有假定的EVH1-和PDZ结合域。由于一些突触后蛋白质具有PDZ结构域（如PSD95和Shank）和EVH1结构域（如Homer），这些蛋白质可能是在突触后位点锚定FAT3的靶点。由于小胶质细胞FAT3表达的时间与突触形成和突触修剪的时间一致，因此小胶质细胞FAT3可能通过异质或同源相互作用不仅调节细胞形态，而且调节突触的形成。由于小胶质细胞不能消除功能性突触，小胶质细胞FAT3可以作为识别功能性突触的传感器。这可能是一个有趣的想法，即神经活动通过FAT3将一些信号传递给小胶质细胞，然后调节适当的突触形成。因此，了解小胶质细胞FAT3的机制可能为阐明与神经回路形成相关的小胶质细胞转变和异质性提供信息线索。

   文章在《中国神经再生研究（英文版）》杂志2021年 12 月 12  期发表。

  https://orcid.org/0000-0002-3471-7654(Fuminori Tsuruta) 

Abstract: Microglia, which comprise approximately 10% of total cells in the brain, are the resident immune cells in the central nervous system and contribute to maintaining the brain homeostasis through monitoring their microenvironment (Kettenmann et al., 2011). Recent studies have reported that microglia also regulate neural circuit formation after birth. The functional transition in microglia has been considered to correlate with their morphological changes over time. Although microglial morphologies were found to be modulated by expressions of particular genes, the mechanisms that underlie morphological changes in microglia have not been fully elucidated. Recently, we have reported that FAT atypical cadherin family protein 3 (FAT3) is a novel factor that stabilizes microglial processes regulated by hypoxanthine (Okajima et al., 2020). Since the timing of FAT3 expression coincides with that of microglial morphological changes during the postnatal stage, it is plausible that FAT3 regulates the microglial transition. In this review, we discuss the biological relevance among microglial heterogeneity and transitions. Moreover, we introduce our recent findings that link FAT3 to the aspect of microglial transition and functions during the postnatal stage.