PUBLICATION
Kif1a and intact microtubules maintain synaptic-vesicle populations at ribbon synapses in zebrafish hair cells
- Authors
- David, S., Pinter, K., Nguyen, K.K., Lee, D.S., Lei, Z., Sokolova, Y., Sheets, L., Kindt, K.S.
- ID
- ZDB-PUB-241008-14
- Date
- 2024
- Source
- The Journal of physiology : (Journal)
- Registered Authors
- Kindt, Katie, Lei, Zhengchang, Pinter, Katherine, Sheets, Lavinia
- Keywords
- hair cells, kinesins, ribbon synapses, sensory systems, synaptic vesicles, zebrafish
- MeSH Terms
-
- Kinesins*/genetics
- Kinesins*/metabolism
- Kinesins*/physiology
- Animals
- Synaptic Vesicles*/metabolism
- Synaptic Vesicles*/physiology
- Microtubules*/metabolism
- Microtubules*/physiology
- Synapses*/metabolism
- Synapses*/physiology
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- Zebrafish Proteins*/physiology
- Hair Cells, Auditory*/metabolism
- Hair Cells, Auditory*/physiology
- Zebrafish
- PubMed
- 39373584 Full text @ J. Physiol.
Citation
David, S., Pinter, K., Nguyen, K.K., Lee, D.S., Lei, Z., Sokolova, Y., Sheets, L., Kindt, K.S. (2024) Kif1a and intact microtubules maintain synaptic-vesicle populations at ribbon synapses in zebrafish hair cells. The Journal of physiology. :.
Abstract
Sensory hair cells of the inner ear utilize specialized ribbon synapses to transmit sensory stimuli to the central nervous system. This transmission necessitates rapid and sustained neurotransmitter release, which depends on a large pool of synaptic vesicles at the hair-cell presynapse. While previous work in neurons has shown that kinesin motor proteins traffic synaptic material along microtubules to the presynapse, the mechanisms of this process in hair cells remain unclear. Our study demonstrates that the kinesin motor protein Kif1a, along with an intact microtubule network, is essential for enriching synaptic vesicles at the presynapse in hair cells. Through genetic and pharmacological approaches, we disrupt Kif1a function and impair microtubule networks in hair cells of the zebrafish lateral-line system. These manipulations led to a significant reduction in synaptic-vesicle populations at the presynapse in hair cells. Using electron microscopy, in vivo calcium imaging, and electrophysiology, we show that a diminished supply of synaptic vesicles adversely affects ribbon-synapse function. Kif1aa mutants exhibit dramatic reductions in spontaneous vesicle release and evoked postsynaptic calcium responses. Furthermore, kif1aa mutants exhibit impaired rheotaxis, a behaviour reliant on the ability of hair cells in the lateral line to respond to sustained flow stimuli. Overall, our results demonstrate that Kif1a-mediated microtubule transport is critical to enrich synaptic vesicles at the active zone, a process that is vital for proper ribbon-synapse function in hair cells. KEY POINTS: Kif1a mRNAs are present in zebrafish hair cells. Loss of Kif1a disrupts the enrichment of synaptic vesicles at ribbon synapses. Disruption of microtubules depletes synaptic vesicles at ribbon synapses. Kif1aa mutants have impaired ribbon-synapse and sensory-system function.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping