Plexin-B1 directly interacts with PDZ-RhoGEF/LARG to regulate RhoA and growth cone morphology
Plexin-B1 directly interacts with PDZ-RhoGEF/LARG to regulate RhoA and growth cone morphology
复制标题
DOI：
10.1016/s0896-6273(02)00750-x
复制
发表时间：
2002-07-03
期刊：
影响因子：
16.2
通讯作者：
Offermanns, S
中科院分区：
文献类型：
--
作者：
Swiercz, JM;Kuner, R;Offermanns, S
丛蛋白是一种广泛表达的跨膜蛋白，在神经系统中介导信号蛋白的排斥信号。然而，丛蛋白介导的信号转导的分子性质仍然知之甚少。在这里，我们证明plexin-B家族成员通过其C末端与Rho鸟嘌呤核苷酸交换因子PDZ-RhoGEF和LARG结合。信号蛋白4D激活丛蛋白b1可调节PDZ-RhoGEF/LARG活性，导致RhoA活化。此外，PDZ-RhoGEF的显性阴性形式可阻断信号素4d诱导的初级海马神经元生长锥塌陷。我们的研究表明，哺乳动物丛状蛋白b家族成员与多结构域蛋白PDZ-RhoGEF和LARG的相互作用代表了丛状蛋白b与局部的、rhog介导的下游信号事件之间的重要分子联系，这些信号事件是丛状蛋白介导的各种细胞现象（包括轴突生长锥塌陷）的基础。
Plexins are widely expressed transmembrane proteins that, in the nervous system, mediate repulsive signals of semaphorins.However, the molecular nature of plexin-mediated signal transduction remains poorly understood. Here, we demonstrate that plexin-B family members associate through their C termini with the Rho guanine nucleotide exchange factors PDZ-RhoGEF and LARG. Activation of plexin-B1 by semaphorin 4D regulates PDZ-RhoGEF/LARG activity leading to RhoA activation. In addition, a dominant-negative form of PDZ-RhoGEF blocks semaphorin 4D-induced growth cone collapse in primary hippocampal neurons. Our study indicates that the interaction of mammalian plexin-B family members with the multidomain proteins PDZ-RhoGEF and LARG represents an essential molecular link between plexin-B and localized, Rho-mediated downstream signaling events which underly various plexin-mediated cellular phenomena including axonal growth cone collapse.