ZFIN ID: ZDB-PUB-041008-12
The Zebrafish nrc Mutant Reveals a Role for the Polyphosphoinositide Phosphatase Synaptojanin 1 in Cone Photoreceptor Ribbon Anchoring
Van Epps, H.A., Hayashi, M., Lucast, L., Stearns, G.W., Hurley, J.B., De Camilli, P., and Brockerhoff, S.E.
Date: 2004
Source: The Journal of neuroscience : the official journal of the Society for Neuroscience   24(40): 8641-8650 (Journal)
Registered Authors: Brockerhoff, Susan, Hurley, James B., Van Epps, Heather
Keywords: ribbon synapse; synaptojanin; retina; cone photoreceptor; zebrafish; sensory neurons
MeSH Terms:
  • Actins/analysis
  • Amino Acid Sequence
  • Animals
  • Larva/anatomy & histology
  • Larva/enzymology
  • Molecular Sequence Data
  • Mutation
  • Nerve Tissue Proteins/genetics
  • Nerve Tissue Proteins/physiology
  • Phenotype
  • Phosphoric Monoester Hydrolases/antagonists & inhibitors
  • Phosphoric Monoester Hydrolases/genetics
  • Phosphoric Monoester Hydrolases/physiology*
  • Retina/anatomy & histology
  • Retina/growth & development
  • Retinal Cone Photoreceptor Cells/chemistry
  • Retinal Cone Photoreceptor Cells/enzymology*
  • Retinal Cone Photoreceptor Cells/ultrastructure*
  • Synaptic Vesicles/ultrastructure*
  • Zebrafish/genetics
  • Zebrafish/growth & development
  • Zebrafish/physiology*
  • Zebrafish Proteins/antagonists & inhibitors
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology*
PubMed: 15470129 Full text @ J. Neurosci.
Visual, vestibular, and auditory neurons rely on ribbon synapses for rapid continuous release and recycling of synaptic vesicles. Molecular mechanisms responsible for the properties of ribbon synapses are mostly unknown. The zebrafish vision mutant nrc has unanchored ribbons and abnormal synaptic transmission at cone photoreceptor synapses. We used positional cloning to identify the nrc mutation as a premature stop codon in the synaptojanin1 (synj1) gene. Synaptojanin 1 (Synj1) is undetectable in nrc extracts, and biochemical activities associated with it are reduced. Furthermore, morpholinos directed against synj1 phenocopy the nrc mutation. Synj1 is a polyphosphoinositide phosphatase important at conventional synapses for clathrin-mediated endocytosis and actin cytoskeletal rearrangement. In the nrc cone photoreceptor pedicle, not only are ribbons unanchored, but synaptic vesicles are reduced in number, abnormally distributed, and interspersed within a dense cytoskeletal matrix. Our findings reveal a new role for Synj1 and link phosphoinositide metabolism to ribbon architecture and function at the cone photoreceptor synapse.