PUBLICATION
Synaptojanin1 is required for temporal fidelity of synaptic transmission in hair cells
- Authors
- Trapani, J.G., Obholzer, N., Mo, W., Brockerhoff, S.E., and Nicolson, T.
- ID
- ZDB-PUB-090511-26
- Date
- 2009
- Source
- PLoS Genetics 5(5): e1000480 (Journal)
- Registered Authors
- Brockerhoff, Susan, Mo, Weike, Nicolson, Teresa, Obholzer, Nikolaus, Trapani, Josef
- Keywords
- Larvae, Vesicles, Action potentials, Synapses, Zebrafish, Cell membranes, Coated vesicles, Inner ear
- MeSH Terms
-
- Alternative Splicing
- Phosphoric Monoester Hydrolases/genetics*
- Phosphoric Monoester Hydrolases/physiology*
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/physiology*
- Microscopy, Electron, Transmission
- Zebrafish/genetics
- Zebrafish/growth & development
- Zebrafish/physiology
- Animals
- Phenotype
- Calcium Channels, L-Type/genetics
- Calcium Channels, L-Type/metabolism
- Hair Cells, Vestibular/pathology
- Hair Cells, Vestibular/physiology*
- Evoked Potentials
- Synaptic Vesicles/pathology
- Synaptic Vesicles/physiology
- Physical Stimulation
- Mutation
- Synaptic Transmission/genetics*
- Synaptic Transmission/physiology*
- Hair Cells, Auditory/pathology
- Hair Cells, Auditory/physiology*
- PubMed
- 19424431 Full text @ PLoS Genet.
Citation
Trapani, J.G., Obholzer, N., Mo, W., Brockerhoff, S.E., and Nicolson, T. (2009) Synaptojanin1 is required for temporal fidelity of synaptic transmission in hair cells. PLoS Genetics. 5(5):e1000480.
Abstract
To faithfully encode mechanosensory information, auditory/vestibular hair cells utilize graded synaptic vesicle (SV) release at specialized ribbon synapses. The molecular basis of SV release and consequent recycling of membrane in hair cells has not been fully explored. Here, we report that comet, a gene identified in an ENU mutagenesis screen for zebrafish larvae with vestibular defects, encodes the lipid phosphatase Synaptojanin 1 (Synj1). Examination of mutant synj1 hair cells revealed basal blebbing near ribbons that was dependent on Cav1.3 calcium channel activity but not mechanotransduction. Synaptojanin has been previously implicated in SV recycling; therefore, we tested synaptic transmission at hair-cell synapses. Recordings of post-synaptic activity in synj1 mutants showed relatively normal spike rates when hair cells were mechanically stimulated for a short period of time at 20 Hz. In contrast, a sharp decline in the rate of firing occurred during prolonged stimulation at 20 Hz or stimulation at a higher frequency of 60 Hz. The decline in spike rate suggested that fewer vesicles were available for release. Consistent with this result, we observed that stimulated mutant hair cells had decreased numbers of tethered and reserve-pool vesicles in comparison to wild-type hair cells. Furthermore, stimulation at 60 Hz impaired phase locking of the postsynaptic activity to the mechanical stimulus. Following prolonged stimulation at 60 Hz, we also found that mutant synj1 hair cells displayed a striking delay in the recovery of spontaneous activity. Collectively, the data suggest that Synj1 is critical for retrieval of membrane in order to maintain the quantity, timing of fusion, and spontaneous release properties of SVs at hair-cell ribbon synapses.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping