Ohira Koji, Homma Koichi J, Hirai Hirohisa, Nakamura Shun, Hayashi Motoharu
Department of Cellular and Molecular Biology, Primate Research Institute, Kyoto University, Aichi, Japan.
Biochem Biophys Res Commun. 2006 Apr 14;342(3):867-74. doi: 10.1016/j.bbrc.2006.02.033. Epub 2006 Feb 20.
Recently, the truncated TrkB receptor, T1, has been reported to be involved in the control of cell morphology via the regulation of Rho proteins, through which T1 binds Rho guanine nucleotide dissociation inhibitor (Rho GDI) 1 and dissociates it in a brain-derived neurotrophic factor (BDNF)-dependent manner. However, it is unclear whether T1 signaling regulates the downstream of Rho signaling and the actin cytoskeleton. In this study, we investigated this question using C6 rat glioma cells, which express T1 endogenously. Rho GDI1 was dissociated from T1 in a BDNF-dependent manner, which also causes decreases in the activities of Rho-signaling molecules such as RhoA, Rho-associated kinase, p21-activated kinase, and extracellular-signal regulated kinase1/2. Moreover, BDNF treatment resulted in the disappearance of stress fibers in the cells treated with lysophosphatidic acid, an activator of RhoA, and in morphological changes in cells. Furthermore, a competitive assay with cyan fluorescent protein fusion proteins of T1-specific sequences reduced the effects of BDNF. These results suggest that T1 regulates the Rho-signaling pathways and the actin cytoskeleton.
最近，据报道，截短型TrkB受体T1通过调控Rho蛋白参与细胞形态的控制，T1以此方式结合Rho鸟嘌呤核苷酸解离抑制剂（Rho GDI）1，并以脑源性神经营养因子（BDNF）依赖的方式使其解离。然而，尚不清楚T1信号是否调节Rho信号的下游及肌动蛋白细胞骨架。在本研究中，我们使用内源性表达T1的C6大鼠胶质瘤细胞来研究这个问题。Rho GDI1以BDNF依赖的方式从T1上解离，这也导致Rho信号分子如RhoA、Rho相关激酶、p21活化激酶和细胞外信号调节激酶1/2的活性降低。此外，BDNF处理导致在用溶血磷脂酸（一种RhoA激活剂）处理的细胞中应力纤维消失，并使细胞形态发生变化。此外，用T1特异性序列的青色荧光蛋白融合蛋白进行的竞争性试验减弱了BDNF的作用。这些结果表明，T1调节Rho信号通路和肌动蛋白细胞骨架。
