Ankyrin-rich membrane spanning protein as a novel modulator of transient receptor potential vanilloid 1-function in nociceptive neurons.

Ankyrin-rich membrane spanning protein as a novel modulator of transient receptor potential vanilloid 1-function in nociceptive neurons.
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DOI:
10.1002/ejp.1008
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发表时间:
2017-07
期刊:
European journal of pain (London, England)
影响因子:
--
通讯作者:
Spahn V
Spahn V
中科院分区:
其他
文献类型:
--
作者:
Peter J;Kasper C;Kaufholz M;Buschow R;Isensee J;Hucho T;Herberg FW;Schwede F;Stein C;Jordt SE;Brackmann M;Spahn V

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离子通道TRPV1主要表达于小直径背根神经节(DRG)神经元,参与急性有害热刺激和化学刺激的感觉。各种信号事件对通道的直接修饰已被深入研究,但对调节大分子TRPV1信号复合物的组成知之甚少。在这里,我们假设新的连接蛋白富含锚蛋白的膜跨越蛋白/激酶D相互作用底物(ARMS)与TRPV1相互作用并调节其在啮齿动物DRG神经元中的功能。我们采用免疫组织化学、电生理、微荧光和免疫沉淀实验来研究TRPV1和ARMS在DRG神经元和转染细胞中的相互作用。我们发现TRPV1和ARMS在DRG神经元亚群中共表达。在转染的HEK 293细胞和小鼠DRG神经元中,ARMS以pka依赖的方式使TRPV1对辣椒素增敏。结合功能成像和免疫细胞化学,我们发现DRG神经元中辣椒素反应的大小不仅取决于TRPV1的表达,还取决于ARMS与TRPV1的共表达。这些数据表明ARMS是调节TRPV1敏感性的信号复合体的重要组成部分。
The ion channel TRPV1 is mainly expressed in small diameter dorsal root ganglion (DRG) neurons, which are involved in the sensation of acute noxious thermal and chemical stimuli. Direct modifications of the channel by diverse signaling events have been intensively investigated, but little is known about the composition of modulating macromolecular TRPV1 signaling complexes. Here, we hypothesize that the novel adaptor protein ankyrin-rich membrane spanning protein/kinase D interacting substrate (ARMS) interacts with TRPV1 and modulates its function in rodent DRG neurons. We used immunohistochemistry, electrophysiology, microfluorimetry and immunoprecipitation experiments to investigate TRPV1 and ARMS interactions in DRG neurons and transfected cells. We found that TRPV1 and ARMS are co-expressed in a subpopulation of DRG neurons. ARMS sensitizes TRPV1 towards capsaicin in transfected HEK 293 cells and in mouse DRG neurons in a PKA-dependent manner. Using a combination of functional imaging and immunocytochemistry, we show that the magnitude of the capsaicin response in DRG neurons depends not only on TRPV1 expression, but on the co-expression of ARMS alongside TRPV1. These data indicate that ARMS is an important component of the signaling complex regulating the sensitivity of TRPV1.
A-激酶锚定蛋白150在TRPV1和CAV 1.2阳性伤害性大鼠背根神经元的特定子集中表达。
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