Transient receptor potential melastatin 3 is a phosphoinositide-dependent ion channel.
Transient receptor potential melastatin 3 is a phosphoinositide-dependent ion channel.
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DOI：
10.1085/jgp.201411336
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发表时间：
2015-07
期刊：
影响因子：
--
通讯作者：
Rohacs T
中科院分区：
文献类型：
--
作者：
Badheka D;Borbiro I;Rohacs T
PI（4，5）P2是TRPM 3活性所必需的，确立了其作为整个TRPM通道家族的关键辅因子的作用。磷酸肌醇是功能多样的瞬时受体电位（TRP）离子通道家族的一般调节剂。磷脂酰肌醇4，5-二磷酸（PI（4，5）P2）已被报道积极调节许多TRP通道，但在一些情况下，磷酸肌醇调节是有争议的。TRP melastatin 3（TRPM 3）是一种热激活的离子通道，也可以被化学激动剂如硫酸双烯醇酮刺激。在这里，我们使用了广泛的方法来确定磷酸肌醇对TRPM 3的影响。我们发现，在切除的由内而外的补丁的通道活动随着时间的推移而下降（rundown），PI（4，5）P2依赖性离子通道的属性。通道活性可以通过应用合成的二辛酰基（diC 8）或天然的花生四烯酸硬脂酰基（AASt）PI（4，5）P2来恢复。PI（4，5）P2前体磷脂酰肌醇4-磷酸（PI（4）P）在恢复通道活性方面不太有效。TRPM 3电流也恢复MgATP，抑制两种不同的磷脂酰肌醇4-激酶抑制剂，或通过预处理与磷脂酰肌醇特异性磷脂酶C（PI-PLC）酶，表明MgATP通过产生磷酸肌醇的作用。在完整细胞中，化学诱导的磷酸肌醇磷酸酶或电压敏感的5′-磷酸酶降低PI（4，5）P2水平抑制通道活性。通过毒蕈碱受体激活PLC也抑制TRPM 3通道活性。总的来说，我们的数据表明，TRPM 3是一个磷酸肌醇依赖性离子通道，PI（4，5）P2丰度的降低限制了其活性。由于TRPM家族的所有其他成员也已被证明需要PI（4，5）P2的活动，我们的数据建立PI（4，5）P2作为该离子通道亚家族的一般正辅因子。
PI(4,5)P2 is required for TRPM3 activity, establishing its role as a crucial cofactor for the entire TRPM channel family. Phosphoinositides are emerging as general regulators of the functionally diverse transient receptor potential (TRP) ion channel family. Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) has been reported to positively regulate many TRP channels, but in several cases phosphoinositide regulation is controversial. TRP melastatin 3 (TRPM3) is a heat-activated ion channel that is also stimulated by chemical agonists, such as pregnenolone sulfate. Here, we used a wide array of approaches to determine the effects of phosphoinositides on TRPM3. We found that channel activity in excised inside-out patches decreased over time (rundown), an attribute of PI(4,5)P2-dependent ion channels. Channel activity could be restored by application of either synthetic dioctanoyl (diC8) or natural arachidonyl stearyl (AASt) PI(4,5)P2. The PI(4,5)P2 precursor phosphatidylinositol 4-phosphate (PI(4)P) was less effective at restoring channel activity. TRPM3 currents were also restored by MgATP, an effect which was inhibited by two different phosphatidylinositol 4-kinase inhibitors, or by pretreatment with a phosphatidylinositol-specific phospholipase C (PI-PLC) enzyme, indicating that MgATP acted by generating phosphoinositides. In intact cells, reduction of PI(4,5)P2 levels by chemically inducible phosphoinositide phosphatases or a voltage-sensitive 5′-phosphatase inhibited channel activity. Activation of PLC via muscarinic receptors also inhibited TRPM3 channel activity. Overall, our data indicate that TRPM3 is a phosphoinositide-dependent ion channel and that decreasing PI(4,5)P2 abundance limits its activity. As all other members of the TRPM family have also been shown to require PI(4,5)P2 for activity, our data establish PI(4,5)P2 as a general positive cofactor of this ion channel subfamily.
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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：
4
作者：
Ingolfsson, Helgi I.;Thakur, Pratima;Herold, Karl F.;Hobart, E. Ashley;Ramsey, Nicole B.;Periole, Xavier;de Jong, Djurre H.;Zwama, Martijn;Yilmaz, Duygu;Hall, Katherine;Maretzky, Thorsten;Hemmings, Hugh C., Jr.;Blobel, Carl;Marrink, Siewert J.;Kocer, Armagan;Sack, Jon T.;Andersen, Olaf S.
通讯作者：
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影响因子：
18.2
作者：
Logothetis DE;Petrou VI;Zhang M;Mahajan R;Meng XY;Adney SK;Cui M;Baki L
通讯作者：
Baki L
DOI：
10.1111/j.1460-9568.2011.07944.x
发表时间：
2012-01
期刊：
The European journal of neuroscience
影响因子：
--
作者：
Hughes S;Pothecary CA;Jagannath A;Foster RG;Hankins MW;Peirson SN
通讯作者：
Peirson SN
影响因子：
4.8
作者：
Klein, Rebecca M.;Ufret-Vincenty, Carmen A.;Gordon, Sharona E.
通讯作者：
Gordon, Sharona E.