TRPM1 is a component of the retinal ON bipolar cell transduction channel in the mGluR6 cascade
TRPM1 is a component of the retinal ON bipolar cell transduction channel in the mGluR6 cascade
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DOI：
10.1073/pnas.0912730107
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发表时间：
2010-01-05
影响因子：
11.1
通讯作者：
Furukawa, Takahisa
中科院分区：
文献类型：
--
作者：
Koike, Chieko;Obara, Takehisa;Furukawa, Takahisa
视网膜双极细胞（BCs）将视觉信号分离为ON和OFF通路是复杂视觉处理的一个重要步骤。光感受器释放的谷氨酸通过代谢谷氨酸受体6 （mGluR6）和调节阳离子通道的G蛋白（Go）调节ON bc的光反应。然而，阳离子通道尚未明确确定。在这里，我们报道了一个小鼠TRPM1长链（TRPM1- l）作为阳离子通道。我们发现TRPM1-L在与mGluR6共定位时局限于ON bc的树突尖端。TRPM1缺失突变小鼠完全失去ON细胞的光响应，但OFF细胞没有。在表达TRPM1-L的细胞中，TRPM1-L作为一个组成活性的非选择性阳离子通道，其活性在mGluR6级联中受到Go的负调控。这些结果表明TRPM1-L是ON BC中mGluR6下游转导通道的一个组成部分。
An essential step in intricate visual processing is the segregation of visual signals into ON and OFF pathways by retinal bipolar cells (BCs). Glutamate released from photoreceptors modulates the photoresponse of ON BCs via metabotropic glutamate receptor 6 (mGluR6) and G protein (Go) that regulates a cation channel. However, the cation channel has not yet been unequivocally identified. Here, we report a mouse TRPM1 long form (TRPM1-L) as the cation channel. We found that TRPM1-L localization is developmentally restricted to the dendritic tips of ON BCs in colocalization with mGluR6. TRPM1 null mutant mice completely lose the photoresponse of ON BCs but not that of OFF BCs. In the TRPM1-L-expressing cells, TRPM1-L functions as a constitutively active nonselective cation channel and its activity is negatively regulated by Go in the mGluR6 cascade. These results demonstrate that TRPM1-L is a component of the ON BC transduction channel downstream of mGluR6 in ON BCs.