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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >Molecular dissection of the semaphorin 4D receptor plexin-B1-stimulated R-Ras GTPase-activating protein activity and neurite remodeling in hippocampal neurons.
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Molecular dissection of the semaphorin 4D receptor plexin-B1-stimulated R-Ras GTPase-activating protein activity and neurite remodeling in hippocampal neurons.

机译：信号量蛋白4D受体plexin-B1刺激海马神经元的R-Ras GTPase活化蛋白活性和神经突重塑的分子解剖。

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摘要

Plexins serve as receptors for repulsive axonal guidance molecules semaphorins. The cytoplasmic domain of the semaphorin 4D (Sema4D) receptor, Plexin-B1 has two separated Ras GTPase-activating protein (GAP)-homologous domains, C1 and C2. Recently, we reported that the Rho family small GTPase Rnd1 associates with Plexin-B1, and the Plexin-B1-Rnd1 complex stimulates GTPase activity of R-Ras, inducing growth cone collapse in hippocampal neurons in response to Sema4D. However, the molecular mechanisms by which Plexin-B1 exhibits the GAP activity remain unclear. In this report, critical roles of Rnd1 and Sema4D in Plexin-B1-stimulated R-Ras GAP activity and neurite remodeling were examined. The N-terminal region of the cytoplasmic domain of Plexin-B1 containing the C1 domain interacts with the C-terminal region containing the C2 domain, and Rnd1 disrupts this interaction. On the other hand, Sema4D induces clustering of Rnd1-bound Plexin-B1, in parallel with inactivation of R-Ras in cells. Antibody clustering of the recombinant cytoplasmic domain of Plexin-B1 in the presence of Rnd1 triggers the R-Ras GAP activity. Deletion of the extracellular domain of Plexin-B1 causes ligand-independent clustering of the receptor, rendering the receptor constitutively active in the presence of Rnd1, and induces contraction of COS-7 cells and inhibition of neurite outgrowth in hippocampal neurons. These results indicate that Rnd1 opens the two R-Ras GAP domains of Plexin-B1, and Sema4D-induced receptor clustering stimulates R-Ras GAP activity and neurite remodeling in hippocampal neurons.
机译：丛蛋白充当排斥性轴突引导分子信号蛋白的受体。信号量4D（Sema4D）受体的细胞质结构域Plexin-B1具有两个分离的Ras GTPase激活蛋白（GAP）同源结构域C1和C2。最近，我们报道了Rho家族的小GTPase Rnd1与Plexin-B1缔合，而Plexin-B1-Rnd1复合物刺激R-Ras的GTPase活性，诱导海马神经元对Sema4D的生长锥塌陷。但是，Plexin-B1表现出GAP活性的分子机制仍不清楚。在本报告中，研究了Rnd1和Sema4D在Plexin-B1刺激的R-Ras GAP活性和神经突重塑中的关键作用。包含C1结构域的Plexin-B1胞质域的N末端区域与包含C2结构域的C末端区域相互作用，而Rnd1破坏这种相互作用。另一方面，Sema4D诱导Rnd1结合的Plexin-B1聚集，同时细胞中R-Ras失活。在Rnd1存在下，Plexin-B1重组胞质域的抗体簇集触发了R-Ras GAP活性。 Plexin-B1胞外域的删除会导致受体的配体独立簇，使受体在Rnd1存在下具有组成性活性，并诱导COS-7细胞收缩并抑制海马神经元的神经突生长。这些结果表明，Rnd1打开了Plexin-B1的两个R-Ras GAP域，并且Sema4D诱导的受体簇刺激了R-Ras GAP活性和海马神经元的神经突重塑。

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