Nociceptive signals induce trafficking of TRPA1 to the plasma membrane.
Nociceptive signals induce trafficking of TRPA1 to the plasma membrane.
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DOI：
10.1016/j.neuron.2009.09.030
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发表时间：
2009-11-25
期刊：
影响因子：
16.2
通讯作者：
Patapoutian, Ardem
中科院分区：
文献类型：
--
作者：
Schmidt, Manuela;Dubin, Adrienne E.;Petrus, Matt J.;Earley, Taryn J.;Patapoutian, Ardem
瞬时受体电位A1(TRPA1)离子通道感受多种伤害性刺激，参与伤害性感受。许多TRPA1激动剂共价修饰该通道并可导致脱敏。修饰的TRPA1的命运和保存其对后续刺激的反应的机制尚不清楚。此外，炎症信号通过未知的方式使涉及蛋白激酶A(PKA)和磷脂酶C(PLC)的TRPA1增敏。我们发现，TRPA1介导的伤害行为可以在体内通过PKA/PLC信号转导和用配基芥子油(MO)激活TRPA1而被敏化。有趣的是，这两种刺激在体外都增加了TRPA1膜的水平。破伤风毒素减弱了神经元对第二次MO脉冲的反应，提示囊泡融合增加了功能表面的TRPA1。电容记录表明，MO可以诱导胞吐。我们认为，TRPA1转位到膜上可能是在急性激活或炎症信号时控制TRPA1功能的机制之一。
Transient receptor potential A1 (TRPA1) ion channel senses a variety of noxious stimuli, and is involved in nociception. Many TRPA1 agonists covalently modify the channel and can lead to desensitization. The fate of modified TRPA1 and the mechanism of preserving its response to subsequent stimuli are not understood. Moreover, inflammatory signals sensitize TRPA1 involving protein kinase A (PKA) and phospholipase C (PLC) through unknown means. We show that TRPA1-mediated nocifensive behavior can be sensitized in vivo via PKA/PLC signaling and by activating TRPA1 with the ligand mustard oil (MO). Interestingly, both stimuli increased TRPA1 membrane levels in vitro. Tetanus toxin attenuated the response to the second of two pulses of MO in neurons, suggesting vesicle-fusion to increase functional surface TRPA1. Capacitance recordings suggest that MO can induce exocytosis. We propose that TRPA1 translocation to the membrane might represent one of the mechanisms controlling TRPA1 functionality upon acute activation or inflammatory signals.
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