Sensitization of TRPA1 by Protein Kinase A.
Sensitization of TRPA1 by Protein Kinase A.
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DOI：
10.1371/journal.pone.0170097
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
McNaughton PA
中科院分区：
文献类型：
--
作者：
Meents JE;Fischer MJ;McNaughton PA
TRPA1离子通道在伤害感受（疼痛敏感）的躯体感觉神经元中表达，并被多种化学刺激物激活，如烟雾中的丙烯醛或芥末中的异硫氰酸酯。在这里，我们研究了由炎症介质引起的TRPA1功能的增强，这被认为在哮喘和COPD等肺部疾病中很重要。蛋白激酶A是一种重要的激酶，作用于炎症介质下游，导致TRPA 1致敏。通过使用定点突变，膜片钳电生理学和钙成像，我们确定四个氨基酸残基，S86，S317，S428和S972，作为PKA介导的磷酸化和致敏的TRPA1的主要目标。
The TRPA1 ion channel is expressed in nociceptive (pain-sensitive) somatosensory neurons and is activated by a wide variety of chemical irritants, such as acrolein in smoke or isothiocyanates in mustard. Here, we investigate the enhancement of TRPA1 function caused by inflammatory mediators, which is thought to be important in lung conditions such as asthma and COPD. Protein kinase A is an important kinase acting downstream of inflammatory mediators to cause sensitization of TRPA1. By using site-directed mutagenesis, patch-clamp electrophysiology and calcium imaging we identify four amino acid residues, S86, S317, S428, and S972, as the principal targets of PKA-mediated phosphorylation and sensitization of TRPA1.