Pikachurin, a dystroglycan ligand, is essential for photoreceptor ribbon synapse formation.
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.
Sato
Shigeru
S
Department of Developmental Biology, Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Osaka, 565-0874, Japan.
Omori
Yoshihiro
Y
Katoh
Kimiko
K
Kondo
Mineo
M
Kanagawa
Motoi
M
Miyata
Kentaro
K
Funabiki
Kazuo
K
Koyasu
Toshiyuki
T
Kajimura
Naoko
N
Miyoshi
Tomomitsu
T
Sawai
Hajime
H
Kobayashi
Kazuhiro
K
Tani
Akiko
A
Toda
Tatsushi
T
Usukura
Jiro
J
Tano
Yasuo
Y
Fujikado
Takashi
T
Furukawa
Takahisa
T
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
D016189:Dystrophin; D016326:Extracellular Matrix Proteins; D005136:Eye Proteins; D008024:Ligands; D049030:Dystroglycans