Mechanical regulation of oligodendrocyte morphology and maturation by the mechanosensor p130Cas
Mechanical regulation of oligodendrocyte morphology and maturation by the mechanosensor p130Cas
复制标题
机械传感器 p130Cas 对少突胶质细胞形态和成熟的机械调节
DOI：
10.1111/jnc.14657
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发表时间：
2019
影响因子：
4.7
通讯作者：
Ikenaka Kazuhiro
中科院分区：
文献类型：
--
作者：
Shimizu Takeshi;Osanai Yasuyuki;Tanaka Kenji F.;Thai Truc Quynh;Abe Manabu;Natsume Rie;Sakimura Kenji;Ikenaka Kazuhiro
少突胶质细胞（OL）是中枢神经系统的髓鞘细胞。最近的研究表明机械因素影响各种细胞特性。机械刺激可以通过整合素、p130Cas、talin 和 vinculin 等机械传感器转化为细胞内生化信号。然而，机械传感器对 OL 进行机械调节的分子机制仍然很大程度上未知。我们发现 OL 的形态受到机械传感器 p130Cas 或 talin1 敲低的影响。 OL 前体细胞的拉伸诱导 p130Cas 的磷酸化和与 talin 相关的纽蛋白组装。剪切应力减少了 OL 过程的数量，而这些效应受到显性失活 (DN) p130Cas 的机械抑制，但不受 DN-talin1 的机械抑制。为了研究 p130Cas 在出生后体内 OLs 中的作用，我们构建了一种新型 p130Cas 敲入小鼠，发现 p130Casin vivo 的过度表达会影响皮质中成熟 OL 的数量。这些结果表明机械传感器 p130Cas 控制 OL 形态发生和成熟。
Oligodendrocytes (OLs) are myelinating cells of the central nervous system. Recent studies have shown that mechanical factors influence various cell properties. Mechanical stimulation can be transduced into intracellular biochemical signals through mechanosensors, such as integrin, p130Cas, talin and vinculin. However, the molecular mechanisms underlying the mechanical regulation of OLs by mechanosensors remain largely unknown. We found that morphology of OL was affected by knockdown of the mechanosensors p130Cas or talin1. Stretching of OL precursor cells induced the phosphorylation of p130Cas and talin‐associated assembly of vinculin. Shear stress decreased the number of OL processes, whereas these effects were mechanically suppressed by dominant‐negative (DN) p130Cas, but not by DN‐talin1. To investigate the roles of p130Cas in post‐natal OLsin vivo, we constructed a novel p130Cas knock‐in mouse and found overexpression of p130Casin vivoaffected the number of mature OLs in the cortex. These results indicate that the mechanosensor p130Cas controls both OL morphogenesis and maturation.