pigk mutation underlies macho behavior and affects Rohon-Beard cell excitability

Carmean, V., Yonkers, M.A., Tellez, M.B., Willer, J.R., Willer, G.B., Gregg, R.G., Geisler, R., Neuhauss, S.C., Ribera, A.B.
Journal of neurophysiology   114(2): 1146-57 (Journal)
Registered Authors
Geisler, Robert, Neuhauss, Stephan, Ribera, Angie, Willer, Greg, Willer, Jason, Yonkers, Marc
GPI-AP, Nav, PigK, Rohon-Beard Cells, touch response
MeSH Terms
  • Action Potentials/physiology
  • Animals
  • Animals, Genetically Modified
  • Cell Adhesion Molecules/genetics
  • Cell Adhesion Molecules/metabolism*
  • Gene Knockdown Techniques
  • Genotyping Techniques
  • Mutation
  • Patch-Clamp Techniques
  • Phenotype
  • Polymerase Chain Reaction
  • RNA, Messenger/metabolism
  • Sensory Receptor Cells/physiology*
  • Sodium/metabolism
  • Touch Perception/genetics
  • Touch Perception/physiology*
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
26133798 Full text @ J. Neurophysiol.
The study of touch-evoked behavior allows investigation of both the cells and circuits that generate a response to tactile stimulation. We investigate a touch-insensitive zebrafish mutant, macho (maco), previously shown to have reduced sodium current amplitude and lack of action potential firing in sensory neurons. In the genomes of mutant but not wild type embryos, we identify a mutation in the pigk gene. The encoded protein, PigK, functions in attachment of glycophosphatidylinositol anchors to precursor proteins. In wild type embryos, pigk mRNA is present at times when mutant embryos display behavioral phenotypes. Consistent with the predicted loss of function induced by the mutation, knock-down of PigK phenocopies maco touch insensitivity and leads to reduced sodium current amplitudes in sensory neurons. We further test whether the genetic defect in pigk underlies the maco phenotype by overexpressing wild-type pigk in mutant embryos. We find that ubiquitous expression of wild type pigk rescues the touch response in maco mutants. In addition, for maco mutants, expression of wild type pigk restricted to sensory neurons rescues sodium current amplitudes and action potential firing in sensory neurons. However, expression of wild type pigk limited to sensory cells of mutant embryos does not allow rescue of the behavioral touch response. Our results demonstrate an essential role for pigk in generation of the touch response beyond that required for maintenance of proper INa density and action potential firing in sensory neurons.
Genes / Markers
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Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes