Essential role of pikachurin, a novel dystroglycan-binding protein, in bipolar dendrite connection to photoreceptor ribbon synapse in the retina

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.