Yu Chuan-Jiang, Gao Yan, Willis Callie L, Li Ping, Tiano Joseph P, Nakamura Paul A, Hyde David R, Li Lei
Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana 46556, USA.
J Neurosci Res. 2007 Feb 15;85(3):488-96. doi: 10.1002/jnr.21157.
Mitogen-associated protein kinase (MAPK)- and protein kinase A (PKA)-dependent signal transductions play important roles in the regulation of gene expression. Both MAPK and PKA pathways can be activated by light exposure. In this study, we investigated the effect of light on MAPK and PKA signal transduction and their roles in the regulation of rhodopsin promoter expression by using transgenic zebrafish [Tg(rhod::GFP)]. The Tg(rhod::GFP) fish express short half-life GFP that is under the transcriptional control of the zebrafish rhodopsin promoter and can therefore be used for in vivo studies of rhodopsin gene transcription in live cells. Blue light plays a role in the regulation of rhodopsin promoter expression via an MAPK-mediated signal transduction cascade. Blue light excites cryptochromes (CRY), which activate the downstream PKC-dependent MAPK signal pathway. White light, on the other hand, regulates rhodopsin promoter expression via a G-protein-coupled cAMP-dependent PKA pathway. White light promotes dopamine release in the retina, which activates dopamine receptors and the downstream PKA pathway. Blocking MAPK signaling diminishes the blue light-induced increases in rhodopsin promoter expression, but this treatment has no effect on white light-mediated rhodopsin promoter expression. Conversely, blocking the PKA pathway diminishes the white light-induced rhodopsin promoter expression but does not affect rhodopsin promoter expression regulated by blue light. Together, the data suggest that MAPK and PKA regulate rhodopsin transcription through parallel signal transduction pathways.
丝裂原活化蛋白激酶（MAPK）和蛋白激酶A（PKA）依赖性信号转导在基因表达调控中发挥重要作用。MAPK和PKA信号通路均可被光照激活。在本研究中，我们利用转基因斑马鱼[Tg(rhod::GFP)]研究了光对MAPK和PKA信号转导的影响及其在视紫红质启动子表达调控中的作用。Tg(rhod::GFP)鱼表达半衰期较短的绿色荧光蛋白（GFP），该蛋白受斑马鱼视紫红质启动子的转录控制，因此可用于活细胞中视紫红质基因转录的体内研究。蓝光通过MAPK介导的信号转导级联反应在视紫红质启动子表达调控中发挥作用。蓝光激活隐花色素（CRY），进而激活下游PKC依赖性MAPK信号通路。另一方面，白光通过G蛋白偶联的cAMP依赖性PKA途径调节视紫红质启动子表达。白光促进视网膜中多巴胺释放，从而激活多巴胺受体和下游PKA途径。阻断MAPK信号传导可减少蓝光诱导的视紫红质启动子表达增加，但该处理对白光介导的视紫红质启动子表达无影响。相反，阻断PKA途径可减少白光诱导的视紫红质启动子表达，但不影响蓝光调节的视紫红质启动子表达。总之，数据表明MAPK和PKA通过平行信号转导途径调节视紫红质转录。
