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          Institute: MPI für Entwicklungsbiologie     Collection: Abteilungsunabhängige Arbeitsgruppen     Display Documents



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ID: 176166.0, MPI für Entwicklungsbiologie / Abteilungsunabhängige Arbeitsgruppen
Gemini encodes a zebrafish L-type calcium channel that localizes at sensory hair cell ribbon synapses
Authors:Sidi, S.; Busch-Nentwich, Elisabeth; Friedrich, R.; Schoenberger, Ulrike; Nicolson, Theresa
Language:English
Date of Publication (YYYY-MM-DD):2004-04
Title of Journal:J Neurosci
Volume:24
Issue / Number:17
Start Page:4213
End Page:4223
Sequence Number of Article:15115817
Review Status:not specified
Audience:Not Specified
Abstract / Description: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.
External Publication Status:published
Document Type:Article
Affiliations:MPI für Entwicklungsbiologie/Abteilungsunabhängige Arbeitsgruppen
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