An optically controlled probe identifies lipid-gating fenestrations within the TRPC3 channel.
An optically controlled probe identifies lipid-gating fenestrations within the TRPC3 channel.
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DOI：
10.1038/s41589-018-0015-6
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发表时间：
2018-04
影响因子：
14.8
通讯作者：
Groschner K
中科院分区：
文献类型：
--
作者：
Lichtenegger M;Tiapko O;Svobodova B;Stockner T;Glasnov TN;Schreibmayer W;Platzer D;de la Cruz GG;Krenn S;Schober R;Shrestha N;Schindl R;Romanin C;Groschner K
瞬时受体电位规范（TRPC）通道TRPC3、TRPC6和TRPC7能够感知脂质信使二酰基甘油（DAG）。这些离子通道中的dag传感和脂质门控过程仍然未知。为了深入了解脂质传感原理，我们制作了一个DAG光开关，OptoDArG，它可以通过光有效地控制TRPC3。TRPC3孔结构域的结构导向诱变筛选揭示了选择性过滤器（G652）后面的单个甘氨酸残基，该残基通过亚基连接开窗暴露于脂质。G652与较大残基的交换改变了TRPC3区分不同DAG分子的能力。通过optodarg介导的光学“脂质钳”对TRPC3通道进行光控激活-失活循环，发现孔域开孔是通道脂质感应机制的关键元件。我们为TRPC通道脂质感知的新概念提供了证据，该通道基于孔域中的侧开孔，可容纳脂质介质来控制门控。
Transient receptor potential canonical (TRPC) channels TRPC3, TRPC6 and TRPC7 are able to sense the lipid messenger diacylglycerol (DAG). The DAG-sensing and lipid-gating processes in these ion channels are still unknown. To gain insights into the lipid-sensing principle, we generated a DAG photoswitch, OptoDArG, that enabled efficient control of TRPC3 by light. A structure-guided mutagenesis screen of the TRPC3 pore domain unveiled a single glycine residue behind the selectivity filter (G652) that is exposed to lipid through a subunit-joining fenestration. Exchange of G652 with larger residues altered the ability of TRPC3 to discriminate between different DAG molecules. Light-controlled activation–deactivation cycling of TRPC3 channels by an OptoDArG-mediated optical ‘lipid clamp’ identified pore domain fenestrations as pivotal elements of the channel´s lipid-sensing machinery. We provide evidence for a novel concept of lipid sensing by TRPC channels based on a lateral fenestration in the pore domain that accommodates lipid mediators to control gating.
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影响因子：
29.4
作者：
Kim MS;Lee KP;Yang D;Shin DM;Abramowitz J;Kiyonaka S;Birnbaumer L;Mori Y;Muallem S
通讯作者：
Muallem S
影响因子：
48
作者：
Barad BA;Echols N;Wang RY;Cheng Y;DiMaio F;Adams PD;Fraser JS
通讯作者：
Fraser JS
DOI：
10.1073/pnas.1612263114
发表时间：
2017-01-03
影响因子：
11.1
作者：
Storch, Ursula;Forst, Anna-Lena;Gudermann, Thomas
通讯作者：
Gudermann, Thomas
影响因子：
5.3
作者：
Dietrich, A;Schnitzler, MMY;Birnbaumer, L
通讯作者：
Birnbaumer, L
影响因子：
4
作者：
Lichtenegger, Michaela;Stockner, Thomas;Groschner, Klaus
通讯作者：
Groschner, Klaus