Activation of the Cl- channel ANO1 by localized calcium signals in nociceptive sensory neurons requires coupling with the IP3 receptor.
Activation of the Cl- channel ANO1 by localized calcium signals in nociceptive sensory neurons requires coupling with the IP3 receptor.
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DOI：
10.1126/scisignal.2004184
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发表时间：
2013-08-27
影响因子：
7.3
通讯作者：
Gamper N
中科院分区：
文献类型：
--
作者：
Jin X;Shah S;Liu Y;Zhang H;Lees M;Fu Z;Lippiat JD;Beech DJ;Sivaprasadarao A;Baldwin SA;Zhang H;Gamper N
我们报道了ANO1（也称为TMEM16A） Ca2+激活的Cl -通道在背根神经节的小神经元中优先被特定的细胞内Ca2+池激活。这些ANO1通道可以被G蛋白偶联受体（GPCR）诱导的Ca2+从细胞内储存的释放选择性激活，但不能被Ca2+通过电压门控Ca2+通道内流激活。这种区分Ca2+池的能力是通过将含有ano1的质膜结构域拴在内质网的近膜区域来实现的，其中也包含gpcr，如缓激肽受体-2和蛋白酶激活受体-2。ANO1的c端和第一个胞内环与IP3R1（肌醇1,4,5-三磷酸受体1）的相互作用促成了系结。膜微域的破坏阻断了ANO1和IP3R1的相互作用，导致GPCR信号与ANO1之间的偶联丧失。连接信号复合物使ano1介导的兴奋响应于特定的Ca2+信号，而不是细胞内Ca2+的全局变化。
We report that ANO1 (also known as TMEM16A) Ca2+-activated Cl− channels in small neurons from dorsal root ganglia are preferentially activated by particular pools of intracellular Ca2+. These ANO1 channels can be selectively activated by the G protein-coupled receptor (GPCR)-induced release of Ca2+ from intracellular stores, but not by Ca2+ influx through voltage-gated Ca2+ channels. This ability to discriminate between Ca2+ pools was achieved by the tethering of ANO1-containing plasma membrane domains, which also contained GPCRs such as bradykinin receptor-2 and protease-activated receptor-2, to juxtamembrane regions of the endoplasmic reticulum. Interaction of the C-terminus and the first intracellular loop of ANO1 with IP3R1 (inositol 1,4,5-trisphosphate receptor 1) contributed to the tethering. Disruption of membrane microdomains blocked the ANO1 and IP3R1 interaction and resulted in the loss of coupling between GPCR signaling and ANO1. The junctional signaling complex enabled ANO1-mediated excitation in response to specific Ca2+ signals rather than to global changes in intracellular Ca2+.
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