A functional coupling between CRMP1 and Nav1.7 for retrograde propagation of Semaphorin3A signaling
A functional coupling between CRMP1 and Nav1.7 for retrograde propagation of Semaphorin3A signaling
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DOI：
10.1242/jcs.199737
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发表时间：
2017-04
影响因子：
4
通讯作者：
Masayuki Yamane;N. Yamashita;Tomonobu Hida;Y. Kamiya;F. Nakamura;P. Kolattukudy;Y. Goshima
中科院分区：
文献类型：
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作者：
Masayuki Yamane;N. Yamashita;Tomonobu Hida;Y. Kamiya;F. Nakamura;P. Kolattukudy;Y. Goshima
Semaphorin 3A（Sema 3A）是一种分泌型轴突导向分子，通过神经纤毛蛋白1（NRP 1）与丛蛋白A（PlexinA）受体的复合物调节轴突的连接。Sema 3A通过河豚毒素（TTX）敏感的PlexA蛋白和原肌球蛋白相关激酶A（TrkA）复合物的逆行轴突运输来调节树突分支。我们在这里证明，Nav1.7（SCN 9A编码），TTX敏感的Na+通道，通过耦合与葡萄糖蛋白反应介导蛋白1（CRMP 1），介导Sema 3A诱导的逆行转运。在小鼠背根神经节（DRG）神经元中，Sema 3A增加PlexA 4和TrkA在生长锥和轴突中的共定位。TTX处理和Nav1.7的RNAi敲低维持了生长锥中Sema 3A诱导的PlexA 4和TrkA的共定位信号，并抑制了PlexA 4和TrkA在远端轴突中的后续定位。在crmp 1 −/− DRG神经元中观察到类似的定位表型。Sema 3A诱导CRMP 1和Nav1.7在生长锥中共定位。与野生型相比，crmp 1 −/−神经元的半最大电压增加。在HEK 293细胞中，CRMP 1的引入降低了共表达外源性Nav1.7的阈值。这些结果表明Nav1.7通过与CRMP 1偶联介导Sema 3A的轴突逆行信号传导。突出显示的文章：与CRMP 1结合，Nav1.7在介导逆行Semaphorin 3A信号传导中发挥作用，突出了其在从神经生长锥到细胞体的信号传导中的功能。
ABSTRACT Semaphorin3A (Sema3A) is a secreted type of axon guidance molecule that regulates axon wiring through complexes of neuropilin-1 (NRP1) with PlexinA protein receptors. Sema3A regulates the dendritic branching through tetrodotoxin (TTX)-sensitive retrograde axonal transport of PlexA proteins and tropomyosin-related kinase A (TrkA) complex. We here demonstrate that Nav1.7 (encoded by SCN9A), a TTX-sensitive Na+ channel, by coupling with collapsin response mediator protein 1 (CRMP1), mediates the Sema3A-induced retrograde transport. In mouse dorsal root ganglion (DRG) neurons, Sema3A increased co-localization of PlexA4 and TrkA in the growth cones and axons. TTX treatment and RNAi knockdown of Nav1.7 sustained Sema3A-induced colocalized signals of PlexA4 and TrkA in growth cones and suppressed the subsequent localization of PlexA4 and TrkA in distal axons. A similar localization phenotype was observed in crmp1−/− DRG neurons. Sema3A induced colocalization of CRMP1 and Nav1.7 in the growth cones. The half maximal voltage was increased in crmp1−/− neurons when compared to that in wild type. In HEK293 cells, introduction of CRMP1 lowered the threshold of co-expressed exogenous Nav1.7. These results suggest that Nav1.7, by coupling with CRMP1, mediates the axonal retrograde signaling of Sema3A. Highlighted Article: Coupled with CRMP1, Nav1.7 plays a role in mediating retrograde Semaphorin 3A signaling, highlighting its function in signaling from the nerve growth cone to cell body.