title: Pikachurin, a dystroglycan ligand, is essential for photoreceptor ribbon synapse formation.
abstract: Exquisitely precise synapse formation is crucial for the mammalian CNS to function correctly. Retinal photoreceptors transfer information to bipolar and horizontal cells at a specialized synapse, the ribbon synapse. We identified pikachurin, an extracellular matrix-like retinal protein, and observed that it localized to the synaptic cleft in the photoreceptor ribbon synapse. Pikachurin null-mutant mice showed improper apposition of the bipolar cell dendritic tips to the photoreceptor ribbon synapses, resulting in alterations in synaptic signal transmission and visual function. Pikachurin colocalized with both dystrophin and dystroglycan at the ribbon synapses. Furthermore, we observed direct biochemical interactions between pikachurin and dystroglycan. Together, our results identify pikachurin as a dystroglycan-interacting protein and demonstrate that it has an essential role in the precise interactions between the photoreceptor ribbon synapse and the bipolar dendrites. This may also advance our understanding of the molecular mechanisms underlying the retinal electrophysiological abnormalities observed in muscular dystrophy patients.
authors.affiliation: Department of Developmental Biology, Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Osaka, 565-0874, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Sato
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Omori
authors.forename: Kimiko
authors.initials: K
authors.lastname: Katoh
authors.forename: Mineo
authors.initials: M
authors.lastname: Kondo
authors.forename: Motoi
authors.initials: M
authors.lastname: Kanagawa
authors.forename: Kentaro
authors.initials: K
authors.lastname: Miyata
authors.forename: Kazuo
authors.initials: K
authors.lastname: Funabiki
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Koyasu
authors.forename: Naoko
authors.initials: N
authors.lastname: Kajimura
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Miyoshi
authors.forename: Hajime
authors.initials: H
authors.lastname: Sawai
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Akiko
authors.initials: A
authors.lastname: Tani
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Toda
authors.forename: Jiro
authors.initials: J
authors.lastname: Usukura
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Tano
authors.forename: Takashi
authors.initials: T
authors.lastname: Fujikado
authors.forename: Takahisa
authors.initials: T
authors.lastname: Furukawa
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D002417:Cattle; D002645:Chickens; D049030:Dystroglycans / Q000378:metabolism*; D016189:Dystrophin / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D005136:Eye Proteins / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D017403:In Situ Hybridization; D008024:Ligands; D008253:Macaca mulatta; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010786:Photoreceptor Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D012160:Retina / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D051245:Retinal Bipolar Cells / Q000166:cytology / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D013569:Synapses / Q000502:physiology*; D015027:Zebrafish
chemical_list: D016189:Dystrophin; D016326:Extracellular Matrix Proteins; D005136:Eye Proteins; D008024:Ligands; D049030:Dystroglycans