感觉神经元中 Cdk5 对 TRPA1 通道活性的调节。
Modulation of TRPA1 channel activity by Cdk5 in sensory neurons.
机构信息
a Department of Human Genetics , University of Chicago , Chicago , IL , USA.
b Department of Biological Sciences , Kent State University , Kent , OH , USA.
出版信息
Channels (Austin). 2018 Jan 1;12(1):65-75. doi: 10.1080/19336950.2018.1424282.
Transient receptor potential cation channel, subfamily A, member 1 (TRPA1), is activated by a broad range of noxious stimuli. Cdk5, a member of the Cdk family, has recently been identified as a modulator of pain signaling pathways. In the current study, we investigated the extent to which Cdk5 modulates TRPA1 activity. Cdk5 inhibition was found to attenuate TRPA1 response to agonist in mouse DRG sensory neurons. Additionally, the presence of active Cdk5 was associated with increased TRPA1 phosphorylation in transfected HEK293 cells that was roscovitine-sensitive and absent in the mouse mutant S449A full-length channel. Immunopurified Cdk5 was observed to phosphorylate human TRPA1 peptide substrate at S448A in vitro. Our results point to a role for Cdk5 in modulating TRPA1 activity.
瞬时受体电位阳离子通道亚家族 A 成员 1（TRPA1）可被多种有害刺激激活。细胞周期蛋白依赖性激酶 5（Cdk5）是细胞周期蛋白依赖性激酶家族的成员，最近被确定为痛觉信号通路的调节剂。在本研究中，我们研究了 Cdk5 调节 TRPA1 活性的程度。发现 Cdk5 抑制可减弱激动剂诱导的小鼠背根神经节感觉神经元中 TRPA1 的反应。此外，在转染的 HEK293 细胞中，活性 Cdk5 的存在与 TRPA1 磷酸化增加有关，这种磷酸化对 roscovitine 敏感，而在小鼠突变体 S449A 全长通道中则不存在。体外观察到免疫纯化的 Cdk5 可使人类 TRPA1 肽底物在 S448A 处发生磷酸化。我们的研究结果表明 Cdk5 在调节 TRPA1 活性方面发挥作用。
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