TRPV1 SUMOylation regulates nociceptive signaling in models of inflammatory pain.
TRPV1 SUMOylation regulates nociceptive signaling in models of inflammatory pain.
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TRPV1 SUMO化调节炎性疼痛模型中的伤害性信号传导
DOI：
10.1038/s41467-018-03974-7
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发表时间：
2018-04-18
影响因子：
16.6
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Wang Y;Gao Y;Tian Q;Deng Q;Wang Y;Zhou T;Liu Q;Mei K;Wang Y;Liu H;Ma R;Ding Y;Rong W;Cheng J;Yao J;Xu TL;Zhu MX;Li Y
尽管瞬时受体电位香草酸亚型1（TRPV1）通道在伤害性热感觉中起着关键作用，但热痛觉过敏的确切机制仍不明确。我们在此报告，在小鼠背根神经节（DRG）神经元中条件性敲除去SUMO化酶SENP1，在角叉菜胶和完全弗氏佐剂诱导的炎症模型中均加剧了热痛觉过敏。TRPV1在C端赖氨酸残基（K822）处发生SUMO化修饰，这一修饰特异性地增强了该通道对热刺激的敏感性，但对辣椒素、质子或电压刺激的敏感性并无增强。SENP1会降低TRPV1的SUMO化水平，而外周炎症则会使其上调。更重要的是，TRPV1敲除小鼠发生炎性热痛觉过敏能力的降低，可通过野生型TRPV1病毒感染腰3/4背根神经节神经元得以恢复，但SUMO化缺陷突变体K822R则无法实现这一点。这些数据表明，TRPV1的SUMO化修饰对于炎性热痛觉过敏的发生至关重要，其机制涉及该通道对热刺激反应的特异性敏化。
SUMO化修饰是一种翻译后修饰。本文作者表明，传递热伤害感受的TRPV1在炎症条件下于背根神经节中发生SUMO化修饰，并促成了小鼠的疼痛行为。
Although TRPV1 channels represent a key player of noxious heat sensation, the precise mechanisms for thermal hyperalgesia remain unknown. We report here that conditional knockout of deSUMOylation enzyme, SENP1, in mouse dorsal root ganglion (DRG) neurons exacerbated thermal hyperalgesia in both carrageenan- and Complete Freund’s adjuvant-induced inflammation models. TRPV1 is SUMOylated at a C-terminal Lys residue (K822), which specifically enhances the channel sensitivity to stimulation by heat, but not capsaicin, protons or voltage. TRPV1 SUMOylation is decreased by SENP1 but upregulated upon peripheral inflammation. More importantly, the reduced ability of TRPV1 knockout mice to develop inflammatory thermal hyperalgesia was rescued by viral infection of lumbar 3/4 DRG neurons of wild-type TRPV1, but not its SUMOylation-deficient mutant, K822R. These data suggest that TRPV1 SUMOylation is essential for the development of inflammatory thermal hyperalgesia, through a mechanism that involves sensitization of the channel response specifically to thermal stimulation. SUMOylation is a post translational modification. Here the authors show that TRPV1, which conveys thermal nociception, is SUMOylated in DRGs in inflammatory conditions and contributes to pain behavior in mice.
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影响因子：
16.2
作者：
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