title: Presynaptic dystroglycan-pikachurin complex regulates the proper synaptic connection between retinal photoreceptor and bipolar cells.
abstract: Dystroglycan (DG) is a key component of the dystrophin-glycoprotein complex (DGC) at the neuromuscular junction postsynapse. In the mouse retina, the DGC is localized at the presynapse of photoreceptor cells, however, the function of presynaptic DGC is poorly understood. Here, we developed and analyzed retinal photoreceptor-specific DG conditional knock-out (DG CKO) mice. We found that the DG CKO retina showed a reduced amplitude and a prolonged implicit time of the ERG b-wave. Electron microscopic analysis revealed that bipolar dendrite invagination into the photoreceptor terminus is perturbed in the DG CKO retina. In the DG CKO retina, pikachurin, a DG ligand in the retina, is markedly decreased at photoreceptor synapses. Interestingly, in the Pikachurin(-/-) retina, the DG signal at the ribbon synaptic terminus was severely reduced, suggesting that pikachurin is required for the presynaptic accumulation of DG at the photoreceptor synaptic terminus, and conversely DG is required for pikachurin accumulation. Furthermore, we found that overexpression of pikachurin induces formation and clustering of a DG-pikachurin complex on the cell surface. The Laminin G repeats of pikachurin, which are critical for its oligomerization and interaction with DG, were essential for the clustering of the DG-pikachurin complex as well. These results suggest that oligomerization of pikachurin and its interaction with DG causes DG assembly on the synapse surface of the photoreceptor synaptic terminals. Our results reveal that the presynaptic interaction of pikachurin with DG at photoreceptor terminals is essential for both the formation of proper photoreceptor ribbon synaptic structures and normal retinal electrophysiology.
authors.affiliation: Department of Developmental Biology, Osaka Bioscience Institute, Osaka, 565-0874, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Omori
authors.forename: Fumiyuki
authors.initials: F
authors.lastname: Araki
authors.forename: Taro
authors.initials: T
authors.lastname: Chaya
authors.forename: Naoko
authors.initials: N
authors.lastname: Kajimura
authors.forename: Shoichi
authors.initials: S
authors.lastname: Irie
authors.forename: Koji
authors.initials: K
authors.lastname: Terada
authors.forename: Yuki
authors.initials: Y
authors.lastname: Muranishi
authors.forename: Toshinori
authors.initials: T
authors.lastname: Tsujii
authors.forename: Shinji
authors.initials: S
authors.lastname: Ueno
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Koyasu
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tamaki
authors.forename: Mineo
authors.initials: M
authors.lastname: Kondo
authors.forename: Shiro
authors.initials: S
authors.lastname: Amano
authors.forename: Takahisa
authors.initials: T
authors.lastname: Furukawa
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D049030:Dystroglycans / Q000378:metabolism*; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D046912:Multiprotein Complexes / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009924:Organ Culture Techniques; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology*; D017729:Presynaptic Terminals / Q000502:physiology*; D051245:Retinal Bipolar Cells / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; D046912:Multiprotein Complexes; D009419:Nerve Tissue Proteins; C553232:pikachurin protein, mouse; D049030:Dystroglycans