A chemokine, SDF-1, reduces the effectiveness of multiple axonal repellents and is required for normal axon pathfinding
A chemokine, SDF-1, reduces the effectiveness of multiple axonal repellents and is required for normal axon pathfinding
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DOI：
10.1523/jneurosci.23-04-01360.2003
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发表时间：
2003-02-15
影响因子：
5.3
通讯作者：
Raper, JA
中科院分区：
文献类型：
--
作者：
Chalasani, SH;Sabelko, KA;Raper, JA
改变神经细胞内环核苷酸的浓度可以显著改变它们对轴突引导线索的反应，但可能引起这种改变的生理信号尚不清楚。在这里，我们表明，趋化因子基质细胞衍生因子1（SDF-1）减少了排斥活动的狭缝-2培养的视网膜神经节细胞轴突，脑信号蛋白3A的背根神经节感觉轴突，和脑信号蛋白3C的交感神经轴突。这是一种调节作用，因为SDF-1本身对视网膜或DRG轴突没有可检测到的吸引或排斥作用。这种调节通过CXCR 4（SDF-1的受体）和百日咳毒素敏感性G蛋白偶联信号通路（诱导cAMP升高）介导。CXCR 4突变小鼠的脊髓含有过度成束和异常投射的轴突。这些结果表明，SDF-1通过环核苷酸依赖性信号通路在调节轴突对各种已知的引导信号的反应中起重要作用。
Altering the concentrations of cyclic nucleotides within nerve cells can dramatically change their responses to axonal guidance cues, but the physiological signals that might induce such alterations are unknown. Here we show that the chemokine stromal cell-derived factor 1 (SDF-1) reduces the repellent activities of slit-2 on cultured retinal ganglion cell axons, of semaphorin 3A on dorsal root ganglion sensory axons, and of semaphorin 3C on sympathetic axons. This is a modulatory effect because SDF-1 has no detectable attractive or repellent effects on retinal or DRG axons by itself. This modulation is mediated through CXCR4, the receptor of SDF-1, and a pertussis toxin-sensitive G-protein-coupled signaling pathway that induces an elevation of cAMP. The spinal cords of CXCR4 mutant mice contain hyperfasciculated and aberrantly projecting axons. These results suggest that SDF-1 plays an essential role in modulating axonal responsiveness to various known guidance cues through a cyclic nucleotide-dependent signaling pathway.