PUBLICATION

Zebrafish Cacna1fa is required for cone photoreceptor function and synaptic ribbon formation

Authors
Jia, S., Muto, A., Orisme, W., Henson, H.E., Parupalli, C., Ju, B., Baier, H., and Taylor, M.R.
ID
ZDB-PUB-140317-41
Date
2014
Source
Human molecular genetics   23(11): 2981-94 (Journal)
Registered Authors
Baier, Herwig, Ju, Bensheng, Muto, Akira, Taylor, Michael R.
Keywords
none
MeSH Terms
  • Adult
  • Animals
  • Calcium Channels, L-Type/genetics
  • Calcium Channels, L-Type/metabolism*
  • Disease Models, Animal
  • Eye Diseases, Hereditary/embryology
  • Eye Diseases, Hereditary/genetics
  • Eye Diseases, Hereditary/metabolism*
  • Female
  • Genetic Diseases, X-Linked/embryology
  • Genetic Diseases, X-Linked/genetics
  • Genetic Diseases, X-Linked/metabolism*
  • Humans
  • Male
  • Myopia/embryology
  • Myopia/genetics
  • Myopia/metabolism*
  • Night Blindness/embryology
  • Night Blindness/genetics
  • Night Blindness/metabolism*
  • Retina/embryology
  • Retina/metabolism
  • Retinal Rod Photoreceptor Cells/metabolism*
  • Synapses/genetics
  • Synapses/metabolism*
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
24419318 Full text @ Hum. Mol. Genet.
Abstract

Mutations in the human CACNA1F gene cause incomplete congenital stationary night blindness type 2 (CSNB2), a non-progressive, clinically heterogeneous retinal disorder. However, the molecular mechanisms underlying CSNB2 have not been fully explored. Here, we describe the positional cloning of a blind zebrafish mutant, wait until dark (wud), which encodes a zebrafish homolog of human CACNA1F. We identified two zebrafish cacna1f paralogs and showed that the cacna1fa transcript (the gene mutated in wud) is expressed exclusively in the photoreceptor layer. We demonstrated that Cacna1fa localizes at the photoreceptor synapse and is absent from wud mutants. Electroretinograms revealed abnormal cone photoreceptor responses from wud mutants, indicating a defect in synaptic transmission. Although there are no obvious morphological differences, we found that wud mutants lacked synaptic ribbons and that wud is essential for the development of synaptic ribbons. We found that Ribeye, the most prominent synaptic ribbon protein, was less abundant and mislocalized in adult wud mutants. In addition to cloning wud, we identified synaptojanin 1 (synj1) as the defective gene in slacker (slak), a blind mutant with floating synaptic ribbons. We determined that Cacna1fa was expressed in slak photoreceptors and that Synj1 was initially expressed wud photoreceptors, but was absent by 5 days postfertilization. Collectively, our data demonstrate that Cacna1fa is essential for cone photoreceptor function and synaptic ribbon formation and reveal a previously unknown yet critical role of L-type voltage-dependent calcium channels in the expression and/or distribution of synaptic ribbon proteins, providing a new model to study the clinical variability in human CSNB2 patients.

Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes