Formation of a new receptor-operated channel by heteromeric assembly of TRPP2 and TRPC1 subunits
Formation of a new receptor-operated channel by heteromeric assembly of TRPP2 and TRPC1 subunits
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DOI：
10.1038/embor.2008.29
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发表时间：
2008-05-01
期刊：
影响因子：
7.7
通讯作者：
Delmas, Patrick
中科院分区：
文献类型：
--
作者：
Bai, Chang-Xi;Giamarchi, Aurelie;Delmas, Patrick
尽管已经报道了瞬时受体电位（TRP）通道之间的几种蛋白质-蛋白质相互作用，但已知它们都仅发生在同一组的成员之间。到目前为止，唯一描述的组间相互作用是TRPP 2和TRPC 1;然而，这种相互作用的意义是未知的。在这里，我们表明，TRPP 2和TRPC 1组装，形成一个独特的星座的新的和TRPP 2/TRPC 1特定的属性的通道。TRPP 2/TRPC 1响应于G蛋白偶联受体活化而活化，并且显示出与单独的TRPP 2或TRPC 1不同的单通道电导、阿米洛利敏感性和离子渗透性的模式。天然TRPP 2/TRPC 1活性在肾细胞中通过互补的功能获得和功能丧失实验显示，并且其在生理条件下的存在通过在初级纤毛处的共定位和通过来自肾膜的免疫共沉淀来支持。异源多聚体TRPP 2/TRPC 1通道的鉴定在机械感觉和基于纤毛的Ca（2+）信号传导中具有意义。
Although several protein-protein interactions have been reported between transient receptor potential (TRP) channels, they are all known to occur exclusively between members of the same group. The only intergroup interaction described so far is that of TRPP2 and TRPC1; however, the significance of this interaction is unknown. Here, we show that TRPP2 and TRPC1 assemble to form a channel with a unique constellation of new and TRPP2/TRPC1-specific properties. TRPP2/TRPC1 is activated in response to G-protein-coupled receptor activation and shows a pattern of single-channel conductance, amiloride sensitivity and ion permeability distinct from that of TRPP2 or TRPC1 alone. Native TRPP2/TRPC1 activity is shown in kidney cells by complementary gain-of-function and loss-of-function experiments, and its existence under physiological conditions is supported by colocalization at the primary cilium and by co-immunoprecipitation from kidney membranes. Identification of the heteromultimeric TRPP2/TRPC1 channel has implications in mechanosensation and cilium-based Ca(2+) signalling.