Pikachurin, a dystroglycan ligand, is essential for photoreceptor ribbon synapse formation

Nat Neurosci. 2008 Aug;11(8):923-31. doi: 10.1038/nn.2160. Epub 2008 Jul 20.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Blotting, Northern
  • Cattle
  • Chickens
  • Dystroglycans / metabolism*
  • Dystrophin / metabolism*
  • Extracellular Matrix / metabolism
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / isolation & purification
  • Extracellular Matrix Proteins / physiology*
  • Eye Proteins / genetics
  • Eye Proteins / isolation & purification
  • Eye Proteins / physiology*
  • Humans
  • In Situ Hybridization
  • Ligands
  • Macaca mulatta
  • Mice
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Molecular Sequence Data
  • Organ Specificity
  • Photoreceptor Cells / cytology
  • Photoreceptor Cells / metabolism
  • Photoreceptor Cells / physiology*
  • Retina / cytology
  • Retina / embryology
  • Retina / metabolism
  • Retinal Bipolar Cells / cytology
  • Retinal Bipolar Cells / physiology*
  • Sequence Homology, Amino Acid
  • Synapses / physiology*
  • Zebrafish

Substances

  • Dystrophin
  • Extracellular Matrix Proteins
  • Eye Proteins
  • Ligands
  • Dystroglycans