Ul-Hussain Mahboob, Zoidl Georg, Klooster Jan, Kamermans Maarten, Dermietzel Rolf
Department of Neuroanatomy and Molecular Brain Research, Ruhr-University Bochum, University Street 150, D-44801 Bochum, Germany.
BMC Mol Biol. 2008 May 27;9:52. doi: 10.1186/1471-2199-9-52.
Changes of the interneuronal coupling mediated by electrical synapse proteins in response to light adaptation and receptive field shaping are a paramount feature in the photoreceptor/horizontal cell/bipolar cell (PRC/HC/BPC) complex of the outer retina. The regulation of these processes is not fully understood at the molecular level but they may require information transfer to the nucleus by locally generated messengers. Electrical synapse proteins may comprise a feasible molecular determinant in such an information-laden signalling pathway.
Connexin55.5 (Cx55.5) is a connexin with horizontal cell-restricted expression in zebrafish accumulating at dendritic sites within the PRC/HC/BPC complex in form of hemichannels where light-dependent plasticity occurs. Here we provide evidence for the generation of a carboxy-terminal domain of Cx55.5. The protein product is translated from the Cx55.5 mRNA by internal translation initiation from an in-frame ATG codon involving a putative internal ribosome entry site (IRES) element localized in the coding region of Cx55.5. This protein product resembling an 11 kDa domain of Cx55.5 is partially located in the nucleus in vivo and in vitro.
Our results demonstrate the generation of a second protein from the coding region of Cx55.5 by an IRES mediated process. The nuclear occurrence of a fraction of this protein provides first evidence that this electrical synapse protein may participate in a putative cytoplasmic to nuclear signal transfer. This suggests that Cx55.5 could be involved in gene regulation making structural plasticity at the PRC/HC/BPC complex feasible.
在视网膜外层的光感受器/水平细胞/双极细胞(PRC/HC/BPC)复合体中,电突触蛋白介导的神经元间耦合响应光适应和感受野塑形的变化是一个至关重要的特征。这些过程在分子水平上的调控尚未完全明了,但它们可能需要通过局部产生的信使将信息传递至细胞核。电突触蛋白可能是这种富含信息的信号通路中一个可行的分子决定因素。
连接蛋白55.5(Cx55.5)是一种在斑马鱼中水平细胞限制性表达的连接蛋白,以半通道的形式聚集在PRC/HC/BPC复合体内的树突部位,而光依赖性可塑性在此发生。在这里,我们提供了Cx55.5羧基末端结构域产生的证据。该蛋白产物是由Cx55.5 mRNA通过内部翻译起始从一个符合读框的ATG密码子翻译而来,该密码子涉及一个位于Cx55.5编码区的假定内部核糖体进入位点(IRES)元件。这种类似于Cx55.5 11 kDa结构域的蛋白产物在体内和体外部分定位于细胞核。
我们的结果表明通过IRES介导的过程从Cx55.5的编码区产生了第二种蛋白质。该蛋白一部分在细胞核中的存在首次证明这种电突触蛋白可能参与了假定的从细胞质到细胞核的信号传递。这表明Cx55.5可能参与基因调控,使得PRC/HC/BPC复合体的结构可塑性成为可能。