Sato Shigeru
Department of Ophthalmology, Higashiosaka City General Hospital. 3-4-5 Nishi-iwata, Higashiosaka-shi, Osaka-fu 578-8588, Japan.
Nippon Ganka Gakkai Zasshi. 2010 Nov;114(11):955-67.
Photoreceptor cells with bipolar cells and horizontal cells form a specialized synapse, the ribbon synapse. We identified the novel retinal extracellular matrix protein pikachurin, and observed that it is localized in the synaptic cleft of the photoreceptor ribbon synapse. In order to investigate the biological functions of pikachurin, we generated a pikachurin knock-out mouse. These mice showed improper apposition of the bipolar cell dendritic tips to the photoreceptor ribbon synapses, alterations of ERG b waves both under scotopic and photopic conditions and attenuation of optokinetic responses. Using immunohistochemistry and pull-down assay, we showed that pikachurin is a novel ligand of alpha-dystroglycan. Our results indicate that the abnormality of interaction between dystrophin and dystroglycan-pikachurin complex may be one cause of the retinal electrophysiological abnormalities observed in Duchenne and Becker muscular dystrophy patients.
光感受器细胞与双极细胞和水平细胞形成一种特殊的突触，即带状突触。我们鉴定出一种新的视网膜细胞外基质蛋白皮卡丘素，并观察到它定位于光感受器带状突触的突触间隙中。为了研究皮卡丘素的生物学功能，我们培育出了一种皮卡丘素基因敲除小鼠。这些小鼠表现出双极细胞树突尖端与光感受器带状突触的对接不当、在暗视和明视条件下视网膜电图b波的改变以及视动反应的减弱。通过免疫组织化学和下拉分析，我们表明皮卡丘素是α- dystroglycan的一种新配体。我们的结果表明，肌营养不良蛋白与dystroglycan - 皮卡丘素复合物之间相互作用的异常可能是杜兴氏和贝克氏肌营养不良症患者视网膜电生理异常的原因之一。
