YAP functions as a mechanotransducer in oligodendrocyte morphogenesis and maturation
YAP functions as a mechanotransducer in oligodendrocyte morphogenesis and maturation
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DOI：
10.1002/glia.23096
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发表时间：
2017-02
期刊：
影响因子：
6.2
通讯作者：
Takeshi Shimizu;Yasuyuki Osanai;Kenji F. Tanaka;M. Abe;R. Natsume;K. Sakimura;K. Ikenaka
中科院分区：
文献类型：
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作者：
Takeshi Shimizu;Yasuyuki Osanai;Kenji F. Tanaka;M. Abe;R. Natsume;K. Sakimura;K. Ikenaka
少突胶质细胞（Oligodendrocytes，OL）是中枢神经系统的髓鞘形成细胞。最近的研究表明，机械因素影响各种细胞特性。机械刺激可以通过机械传感器和细胞内机械转换器（如雅普）转换成细胞内生化信号。然而，雅普对OLs机械调控的分子机制仍不清楚。我们发现敲低雅普会影响OL的形态以及OL与神经元轴突之间的相互作用。OL前体细胞的机械拉伸诱导核雅普积累和粘着斑组装，这是机械转导的关键平台。剪切应力减少了OL过程的数量，而显性负性形式的雅普抑制了这些作用。为了研究雅普在体内出生后OL中的作用，我们构建了一种新的雅普敲入小鼠，发现体内过表达雅普广泛影响OL成熟。这些结果表明，雅普调节OL形态和成熟的机械因素。GLIA 2017;65：360-374
Oligodendrocytes (OLs) are myelinating cells of the central nervous system. Recent studies have shown that mechanical factors influence various cell properties. Mechanical stimuli can be transduced into intracellular biochemical signals through mechanosensors and intracellular mechanotransducers, such as YAP. However, the molecular mechanisms underlying mechanical regulation of OLs by YAP remain unknown. We found that OL morphology and interactions between OLs and neuronal axons were affected by knocking down YAP. Mechanical stretching of OL precursor cells induced nuclear YAP accumulation and assembly of focal adhesion, key platforms for mechanotransduction. Shear stress decreased the number of OL processes, whereas a dominant‐negative form of YAP suppressed these effects. To investigate the roles of YAP in postnatal OLs in vivo, we constructed a novel YAP knock‐in mouse and found that in vivo overexpression of YAP widely affected OL maturation. These results indicate that YAP regulates OL morphology and maturation in response to mechanical factors. GLIA 2017;65:360–374