Differential regulation of proton-sensitive ion channels by phospholipids: a comparative study between ASICs and TRPV1.
Differential regulation of proton-sensitive ion channels by phospholipids: a comparative study between ASICs and TRPV1.
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DOI：
10.1371/journal.pone.0122014
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Suh BC
中科院分区：
文献类型：
--
作者：
Kweon HJ;Yu SY;Kim DI;Suh BC
质子在产生疼痛的病理条件下释放，如炎症、缺血性中风、感染和癌症。在正常的突触活动中，质子被认为在神经传递过程中发挥作用。酸敏感离子通道（Acid-sensing ion channels，ASIC）是中枢神经系统（central nervous system，CNS）和外周神经系统（peripheral nervous system，PNS）中典型的质子感受器。除了ASIC，辣椒素和热激活的瞬时受体电位香草酸1（TRPV 1）通道也可以介导质子介导的疼痛信号。尽管它们在感知pH波动方面很重要，但这些质子敏感离子通道的调节机制仍需要进一步研究。在这里，我们比较了ASICs和TRPV 1的调节膜磷酸肌醇，这是许多受体和离子通道的一般辅因子。我们观察到ASIC不需要膜磷脂酰肌醇4-磷酸（PI（4）P）或磷脂酰肌醇4，5-二磷酸（PI（4，5）P2）来实现其功能。PI（4）P和PI（4，5）P2同时阻断TRPV 1电流，则TRPV 1电流被抑制。通过使用一种新型嵌合蛋白CF-PTEN，该蛋白可以在3，4，5-三磷酸磷脂酰肌醇（PI（3，4，5）P3）的D3位置特异性去磷酸化，我们还观察到ASIC和TRPV 1活性都没有因完整细胞中PI（3，4，5）P3的耗尽而改变。最后，我们比较了花生四烯酸（AA）对两种质子敏感离子通道的作用。我们观察到AA增强ASIC和TRPV 1的电流，但它们具有不同的恢复方面。总之，ASIC和TRPV 1对膜磷脂如PI（4）P、PI（4，5）P2和AA具有不同的敏感性，尽管它们作为质子传感器具有共同的作用。进一步研究ASICs和TRPV 1在质子介导的信号转导中的互补作用和各自的贡献是必要的。
Protons are released in pain-generating pathological conditions such as inflammation, ischemic stroke, infection, and cancer. During normal synaptic activities, protons are thought to play a role in neurotransmission processes. Acid-sensing ion channels (ASICs) are typical proton sensors in the central nervous system (CNS) and the peripheral nervous system (PNS). In addition to ASICs, capsaicin- and heat-activated transient receptor potential vanilloid 1 (TRPV1) channels can also mediate proton-mediated pain signaling. In spite of their importance in perception of pH fluctuations, the regulatory mechanisms of these proton-sensitive ion channels still need to be further investigated. Here, we compared regulation of ASICs and TRPV1 by membrane phosphoinositides, which are general cofactors of many receptors and ion channels. We observed that ASICs do not require membrane phosphatidylinositol 4-phosphate (PI(4)P) or phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) for their function. However, TRPV1 currents were inhibited by simultaneous breakdown of PI(4)P and PI(4,5)P2. By using a novel chimeric protein, CF-PTEN, that can specifically dephosphorylate at the D3 position of phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3), we also observed that neither ASICs nor TRPV1 activities were altered by depletion of PI(3,4,5)P3 in intact cells. Finally, we compared the effects of arachidonic acid (AA) on two proton-sensitive ion channels. We observed that AA potentiates the currents of both ASICs and TRPV1, but that they have different recovery aspects. In conclusion, ASICs and TRPV1 have different sensitivities toward membrane phospholipids, such as PI(4)P, PI(4,5)P2, and AA, although they have common roles as proton sensors. Further investigation about the complementary roles and respective contributions of ASICs and TRPV1 in proton-mediated signaling is necessary.
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影响因子：
16.2
作者：
Cao E;Cordero-Morales JF;Liu B;Qin F;Julius D
通讯作者：
Julius D
影响因子：
64.8
作者：
Chyb, S;Raghu, P;Hardie, RC
通讯作者：
Hardie, RC
影响因子：
5.3
作者：
DUBRIDGE, RB;TANG, P;CALOS, MP
通讯作者：
CALOS, MP
影响因子：
64.8
作者：
Chuang, HH;Prescott, ED;Julius, D
通讯作者：
Julius, D
DOI：
10.1073/pnas.1407018111
发表时间：
2014-06-17
影响因子：
11.1
作者：
Du, Jianyang;Reznikov, Leah R.;Welsh, Michael J.
通讯作者：
Welsh, Michael J.