瞬时受体电位阳离子通道亚家族 M 成员 1（TRPM1）是 mGluR6 级联中视网膜 ON 双极细胞转导通道的一个组成部分。
TRPM1 is a component of the retinal ON bipolar cell transduction channel in the mGluR6 cascade.
机构信息
Department of Developmental Biology, Osaka Bioscience Institute, Osaka 565-0874, Japan.
出版信息
Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):332-7. doi: 10.1073/pnas.0912730107. Epub 2009 Dec 4.
Abstract
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.
摘要
在复杂的视觉处理中，一个重要的步骤是通过视网膜双极细胞 (BC) 将视觉信号分离为 ON 和 OFF 通路。光感受器释放的谷氨酸通过代谢型谷氨酸受体 6 (mGluR6) 和 G 蛋白 (Go) 调节阳离子通道来调节 ON BC 的光反应。然而，阳离子通道尚未得到明确鉴定。在这里，我们报告了一种作为阳离子通道的小鼠 TRPM1 长形式 (TRPM1-L)。我们发现，TRPM1-L 的定位在发育上仅限于 ON BC 的树突末梢，与 mGluR6 共定位。TRPM1 缺失突变小鼠完全丧失了 ON BC 的光反应，但不影响 OFF BC 的光反应。在 TRPM1-L 表达细胞中，TRPM1-L 作为组成型激活的非选择性阳离子通道发挥作用，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 转导通道的组成部分，位于 mGluR6 下游的 ON BC 中。
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