Biogenesis of GPI-anchored proteins is essential for surface expression of sodium channels in zebrafish Rohon-Beard neurons to respond to mechanosensory stimulation

Nakano, Y., Fujita, M., Ogino, K., Saint-Amant, L., Kinoshita, T., Oda, Y., and Hirata, H.
Development (Cambridge, England)   137(10): 1689-1698 (Journal)
Registered Authors
Hirata, Hiromi, Oda, Yoichi, Saint-Amant, Louis
Zebrafish, Sodium channel, Behavior, Rohon-Beard neuron, GPI-anchored protein, GPI transamidase, Touch response
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Antigens, Surface/metabolism
  • CHO Cells
  • Cell Death/drug effects
  • Cell Death/genetics
  • Cell Death/physiology
  • Cricetinae
  • Cricetulus
  • Embryo, Nonmammalian
  • Gene Knockdown Techniques
  • Glycosylphosphatidylinositols/biosynthesis
  • Glycosylphosphatidylinositols/metabolism*
  • Mechanotransduction, Cellular/genetics*
  • Membrane Proteins/biosynthesis*
  • Membrane Proteins/metabolism
  • Membrane Proteins/physiology
  • Physical Stimulation
  • RNA, Small Interfering/pharmacology
  • Sensory Receptor Cells/drug effects
  • Sensory Receptor Cells/metabolism*
  • Sensory Receptor Cells/physiology
  • Sodium Channels/metabolism*
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Zebrafish/metabolism
20392743 Full text @ Development
In zebrafish, Rohon-Beard (RB) neurons are primary sensory neurons present during the embryonic and early larval stages. At 2 days post-fertilization (dpf), wild-type zebrafish embryos respond to mechanosensory stimulation and swim away from the stimuli, whereas mi310 mutants are insensitive to touch. During approximately 2-4 dpf, wild-type RB neurons undergo programmed cell death, which is caused by sodium current-mediated electrical activity, whereas mutant RB cells survive past 4 dpf, suggesting a defect of sodium currents in the mutants. Indeed, electrophysiological recordings demonstrated the generation of action potentials in wild-type RB neurons, whereas mutant RB cells failed to fire owing to the reduction of voltage-gated sodium currents. Labeling of dissociated RB neurons with an antibody against voltage-gated sodium channels revealed that sodium channels are expressed at the cell surface in wild-type, but not mutant, RB neurons. Finally, in mi310 mutants, we identified a mis-sense mutation in pigu, a subunit of GPI (glycosylphosphatidylinositol) transamidase, which is essential for membrane anchoring of GPI-anchored proteins. Taken together, biogenesis of GPI-anchored proteins is necessary for cell surface expression of sodium channels and thus for firings of RB neurons, which enable zebrafish embryos to respond to mechanosensory stimulation.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes