ZFIN ID: ZDB-PUB-040505-5
gemini encodes a zebrafish L-type calcium channel that localizes at sensory hair cell ribbon synapses
Sidi, S., Busch-Nentwich, E., Friedrich, R., Schoenberger, U., and Nicolson, T.
Date: 2004
Source: The Journal of neuroscience : the official journal of the Society for Neuroscience   24(17): 4213-4223 (Journal)
Registered Authors: Busch-Nentwich, Elisabeth, Friedrich, Rainer, Nicolson, Teresa, Sidi, Samuel
Keywords: gemini, L-type calcium channels, deafness, hair cell, ribbon synapse, microphonics, synaptic transmission
MeSH Terms:
  • Amino Acid Sequence
  • Animals
  • Calcium Channels, L-Type/biosynthesis*
  • Calcium Channels, L-Type/genetics
  • Cell Membrane/metabolism
  • Cell Membrane/ultrastructure
  • Deafness/genetics
  • Deafness/physiopathology
  • Hair Cells, Auditory/cytology
  • Hair Cells, Auditory/metabolism*
  • Larva
  • Molecular Sequence Data
  • Phenotype
  • Phylogeny
  • Point Mutation
  • Protein Isoforms/biosynthesis
  • Protein Isoforms/genetics
  • Synapses/metabolism*
  • Synapses/ultrastructure
  • Vestibular Diseases/genetics
  • Vestibular Diseases/physiopathology
  • Zebrafish/physiology*
PubMed: 15115817 Full text @ J. Neurosci.
L-type Ca2+ channels (LTCCs) drive the bulk of voltage-gated Ca2+ entry in vertebrate inner ear hair cells (HCs) and are essential for mammalian auditory processing. LTCC currents have been implicated in neurotransmitter release at the HC afferent active zone, the ribbon synapse. It is likely that LTCCs play a direct role in vesicle fusion; however, the subcellular localization of the channels in HCs has not been fully resolved. Via positional cloning, we show that mutations in a zebrafish LTCC encoding gene, cav1.3a, underlie the auditory-vestibular defects of gemini (gem) circler mutants. gem homozygous receptor mutant HCs display normal cell viability, afferent synaptogenesis, and peripheral innervation, yet exhibit strongly reduced extracellular potentials (approximately 50% of wild-type potentials). Apical FM1-43 uptake, however, is unaffected in gem mutant HCs, suggesting that mechanotransduction channels are functional. Using a Gem-specific antibody, we show that the bulk of Gem/Ca(v)1.3a immunoreactivity in HCs is restricted to basally located focal spots. The number and location of focal spots relative to nerve terminals, and their remarkable ring-shaped structure, which is reminiscent of synaptic dense bodies, are consistent with Gem/Ca(v)1.3a channels clustering at HC ribbon synapses.