Bönigk W, Müller F, Middendorff R, Weyand I, Kaupp U B
Institut für Biologische Informationsverarbeitung, Forschungszentrum Jülich, Germany.
J Neurosci. 1996 Dec 1;16(23):7458-68. doi: 10.1523/JNEUROSCI.16-23-07458.1996.
Light sensitivity of the pineal has been retained in most vertebrates, except mammals. Retinal photoreceptors and pinealocytes share common components of light-dependent signaling pathways. In particular, an ion channel gated by cGMP has been electrophysiologically identified in chick pinealocytes; however, the physiological function of a light-sensitive enzyme cascade is not known, and primary structures of only a few pineal components have been determined. By PCR analysis and cloning of the respective cDNA, we show that the chick pineal expresses the alpha-subunit of the cyclic nucleotide-gated (CNG) channel of rod photoreceptors and two short forms of the cone CNG channel. Analysis of the chick cone CNG channel gene reveals that these forms are produced by alternative splicing, which removes either one or two exons from the transcript. The shorter splice variant is functional when heterologously expressed, and it is approximately twofold more sensitive to activation by cGMP than the cone CNG channel. The chick cone CNG channel and the pineal splice form are both modulated by Ca2+/calmodulin (CaM). The CaM sensitivity might be mediated by a putative CaM-binding site in an N-terminal segment encoded by exon 4. This exon is missing in the gene for the rod CNG channel alpha-subunit. Pineal CNG channels are candidates for receptor-mediated Ca2+ entry into pinealocytes and may be an important element of signaling pathways that control the light response and secretion of the pineal hormone melatonin.
除哺乳动物外，大多数脊椎动物的松果体都保留了对光的敏感性。视网膜光感受器和松果体细胞共享光依赖信号通路的共同成分。特别是，在鸡松果体细胞中已通过电生理学方法鉴定出一种由环鸟苷酸（cGMP）门控的离子通道；然而，光敏感酶级联反应的生理功能尚不清楚，仅确定了少数松果体成分的一级结构。通过聚合酶链反应（PCR）分析和各自互补脱氧核糖核酸（cDNA）的克隆，我们发现鸡松果体表达视杆光感受器环核苷酸门控（CNG）通道的α亚基和两种短形式的视锥CNG通道。对鸡视锥CNG通道基因的分析表明，这些形式是通过可变剪接产生的，可变剪接会从转录本中去除一个或两个外显子。较短的剪接变体在异源表达时具有功能，并且它对cGMP激活的敏感性比视锥CNG通道高约两倍。鸡视锥CNG通道和松果体剪接形式均受Ca2+/钙调蛋白（CaM）调节。CaM敏感性可能由外显子4编码的N端片段中的一个假定CaM结合位点介导。该外显子在视杆CNG通道α亚基的基因中缺失。松果体CNG通道是受体介导的Ca2+进入松果体细胞的候选者，可能是控制光反应和松果体激素褪黑素分泌的信号通路的重要组成部分。
