Tanno Toshihiko, Fujiwara Ayumi, Sakaguchi Kunihiko, Tanaka Katsuhiro, Takenaka Shigeo, Tsuyama Shingo
Department of Veterinary Science, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan.
FEBS Lett. 2007 Mar 6;581(5):1022-6. doi: 10.1016/j.febslet.2007.02.001. Epub 2007 Feb 12.
Three slit genes, slit1 to slit3, have been cloned to date. Slit1 and slit2 act as chemorepellent factors for axon guidance. Slit3 is involved in the formation of the diaphragm and kidney during embryogenesis. However, its molecular function remains unclear. We found that slit3 expression was induced by lipopolysaccharide (LPS)-stimulation in macrophages and that it was localized in the mitochondria and along the plasma membrane. Silencing of slit3 expression by RNA interference reduced cell motility and Rac/Cdc42 activation. These results suggest that slit3 functions as an intracellular signaling molecule for cell motility as part of the LPS-induced signaling cascade.
迄今为止,已克隆出三个 slit 基因,即 slit1 至 slit3。Slit1 和 Slit2 作为轴突导向的化学排斥因子发挥作用。Slit3 在胚胎发育过程中参与膈肌和肾脏的形成。然而,其分子功能仍不清楚。我们发现,巨噬细胞经脂多糖(LPS)刺激后可诱导 slit3 表达,且其定位于线粒体和沿质膜分布。通过 RNA 干扰使 slit3 表达沉默可降低细胞运动性以及 Rac/Cdc42 激活。这些结果表明,slit3 作为 LPS 诱导信号级联反应的一部分,作为细胞运动性的细胞内信号分子发挥作用。