TRPV2 Enhances Axon Outgrowth through Its Activation by Membrane Stretch in Developing Sensory and Motor Neurons
TRPV2 Enhances Axon Outgrowth through Its Activation by Membrane Stretch in Developing Sensory and Motor Neurons
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DOI：
10.1523/jneurosci.5830-09.2010
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发表时间：
2010-03-31
影响因子：
5.3
通讯作者：
Tominaga, Makoto
中科院分区：
文献类型：
--
作者：
Shibasaki, Koji;Murayama, Namie;Tominaga, Makoto
热敏TRP （thermo TRP）通道因其对感觉转导的贡献而被广泛认可，响应各种刺激，包括温度、伤害性刺激、触摸和渗透压。然而，热TRP通道在发育过程中的确切作用尚未确定。为了探讨热TRP通道在神经发育过程中的功能重要性，我们测定了胚胎小鼠的时间表达。有趣的是，从胚胎10.5天开始，除了背根神经节外，脊髓运动神经元中也检测到TRPV2的表达，并且定位于轴突轴和生长锥，这表明该通道对轴突生长调节很重要。我们发现内源性TRPV2在发育神经元中以膜拉伸依赖的方式被激活，通过TRPV2和TRPV2特异性shRNA的显性阴性抑制TRPV2的功能，并显著促进轴突的生长。因此，我们首次揭示了TRPV2在发育过程中通过膜拉伸激活轴突生长是一个重要的调节剂。
Thermosensitive TRP (thermo TRP) channels are well recognized for their contributions to sensory transduction, responding to a wide variety of stimuli including temperature, nociceptive stimuli, touch, and osmolarity. However, the precise roles for the thermo TRP channels during development have not been determined. To explore the functional importance of thermo TRP channels during neural development, the temporal expression was determined in embryonic mice. Interestingly, TRPV2 expression was detected in spinal motor neurons in addition to the dorsal root ganglia from embryonic day 10.5 and was localized in axon shafts and growth cones, suggesting that the channel is important for axon outgrowth regulation. We revealed that endogenous TRPV2 was activated in a membrane stretch-dependent manner in developing neurons by knocking down the TRPV2 function with dominant-negative TRPV2 and TRPV2-specific shRNA and significantly promoted axon outgrowth. Thus, for the first time we revealed that TRPV2 is an important regulator for axon outgrowth through its activation by membrane stretch during development.