RanBPM contributes to Semaphorin3A signaling through plexin-A receptors
RanBPM contributes to Semaphorin3A signaling through plexin-A receptors
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DOI：
10.1523/jneurosci.0704-06.2006
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发表时间：
2006-05-03
影响因子：
5.3
通讯作者：
Strittmatter, SM
中科院分区：
文献类型：
--
作者：
Togashi, H;Schmidt, EF;Strittmatter, SM
已知分泌的 Semaphorin3A (Sema3A) 蛋白在神经系统发育过程中充当可扩散和排斥性的轴突引导信号。由 Neuropilin 和 Plexin-A 组成的受体复合物介导它们的作用。尽管有文献报道涉及塌陷素反应介导蛋白和与 CasL 蛋白 (MICAL) 相互作用的分子作为 Plexin-A 激活的介导物，但 Plexin-A 信号转导的定义仍然不明确。在这里，我们定义了重构环境中 Sema3A 信号传导所需的 Plexin-A1 结构域，然后搜索与该结构域相互作用的蛋白质。 RanBPM 显示与 Plexin-A1 发生物理相互作用，并且 RanBPM/Plexin 复合物受 MICAL 表达调节。 RanBPM 的过度表达与 PlexinA1 协同作用，减少非神经元细胞扩散，并在体外和体内强烈抑制轴突生长。截短的 RanBPM 蛋白可阻断非神经元和神经元细胞中的 Sema3A 反应。 RanBPM 表达的抑制会降低 Sema3A 的反应性。因此，RanBPM 是通过 Plexin-A 的 Sema3A 信号传导的介体。 RanBPM 具有将 Plexin-A 受体与轴突引导中的逆行运输和微管功能联系起来的潜力。
Secreted Semaphorin3A (Sema3A) proteins are known to act as diffusible and repellant axonal guidance cues during nervous system development. A receptor complex consisting of a Neuropilin and a Plexin-A mediates their effects. Plexin-A signal transduction has remained poorly defined despite the documented involvement of collapsin response mediator protein and molecule interacting with CasL proteins (MICALs) as mediators of Plexin-A activation. Here, we defined a domain of Plexin-A1 required for Sema3A signaling in a reconstituted environment and then searched for proteins interacting with this domain. RanBPM is shown to physically interact with Plexin-A1, and the RanBPM/Plexin complex is regulated by MICAL expression. Overexpression of RanBPM cooperates with PlexinA1 to reduce non-neuronal cell spreading and strongly inhibit axonal outgrowth in vitro and in vivo. A truncated RanBPM protein blocks Sema3A responsiveness in non-neuronal and neuronal cells. Suppression of RanBPM expression reduces Sema3A responsiveness. Thus, RanBPM is a mediator of Sema3A signaling through Plexin-A. RanBPM has the potential to link Plexin-A receptors to retrograde transport and microtubule function in axonal guidance.