Type
Text
Type
Dissertation
Advisor
Howard Sirotkin | Matthews, Gary G. | Steve Yazulla | Ruth Heidelberger.
Date
2010-12-01
Keywords
Neurosciences | auditory, exocytosis, presynaptic terminal, sensory, stereocilia, visual
Department
Department of Neuroscience
Language
en_US
Source
This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree.
Identifier
http://hdl.handle.net/11401/72725
Publisher
The Graduate School, Stony Brook University: Stony Brook, NY.
Format
application/pdf
Abstract
The primary receptor cells of the visual, auditory, vestibular and lateral line systems encode a broad range of sensory information by modulating the tonic release of the neurotransmitter glutamate in response to graded changes in membrane potential. The output synapses of these neurons are marked by structures called synaptic ribbons, which tether a pool of releasable synaptic vesicles at the active zone. Despite the importance of the ribbon in synaptic transmission, the molecular mechanisms that govern the assembly and function of the exocytotic machinery in these terminals are poorly understood. We have identified a subfamily of SNARE complex regulators, composed of complexin 3 and complexin 4, which are enriched in ribbon-containing sensory neurons. Phylogenetic analysis reveals that there are two complexin 3 paralogs and three complexin 4 paralogs in zebrafish. Complexin 3/4 is rapidly targeted to photoreceptor presynaptic terminals in the zebrafish retina and pineal organ concomitantly with RIBEYE, a member of the CtBP family of transcriptional corepressors that is the major component of ribbons. In hair cells of the inner ear and lateral line, however, complexin 3/4 immunoreactivity clusters on the apical surfaces of hair cells, among their stereocilia. While a complexin 4a-specific antibody and riboprobe selectively label visual system ribbon-containing neurons, neuromasts and the inner ear contain complexin 4b. Complexin 4a knockdown in vivo perturbs visual background adaptation and optokinetic responses, indicating that these mutants are blind, without grossly affecting photoreceptor presynaptic architecture. Complexins may have additional functions during development since modulation of complexin 3a levels via knockdown or overexpression induces pleiotropic effects on dorsoventral patterning and eye development. Taken together, these results provide evidence for the concurrent transport and/or assembly of multiple components of the active zone in developing ribbon terminals. Members of the complexin 3/4 subfamily are enriched in these terminals in the visual system and in hair bundles of the octavolateral system, suggesting that these proteins are differentially targeted and have multiple roles in ribbon-containing sensory neurons. Furthermore, these results implicate complexin 3 and complexin 4 as candidate genes for hereditary visual, auditory, and vestibular disorders.
Recommended Citation
Zanazzi, George, "Targeting and roles of complexins in zebrafish ribbon-containing neurons" (2010). Stony Brook Theses and Dissertations Collection, 2006-2020 (closed to submissions). 1928.
https://commons.library.stonybrook.edu/stony-brook-theses-and-dissertations-collection/1928