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Synaptic mitochondria regulate hair-cell synapse size and function
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DOI：10.7554/eLife.48914.png)
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Sensory hair cells in the ear utilize specialized ribbon synapses. These synapses are defined by electron-dense presynaptic structures called ribbons, composed primarily of the structural protein Ribeye. Previous work has shown that voltage-gated influx of Ca2+ through Ca(V)1.3 channels is critical for hair-cell synapse function and can impede ribbon formation. We show that in mature zebrafish hair cells, evoked presynaptic-Ca2+ influx through Ca(V)1.3 channels initiates mitochondrial-Ca2+ (mito-Ca2+) uptake adjacent to ribbons. Block of mito-Ca2+ uptake in mature cells depresses presynaptic-Ca2+ influx and impacts synapse integrity. In developing zebrafish hair cells, mito-Ca2+ uptake coincides with spontaneous rises in presynaptic-Ca2+ influx. Spontaneous mito-Ca2+ loading lowers cellular NAD(+)/NADH redox and downregulates ribbon size. Direct application of NAD(+) or NADH increases or decreases ribbon size respectively, possibly acting through the NAD(H)-binding domain on Ribeye. Our results present a mechanism where presynaptic- and mito-Ca2+ couple to confer proper presynaptic function and formation.
Keyword:
INTRACELLULAR CALCIUM REGULATION
BINDING-PROTEIN
SPATIAL GRADIENTS
ACTION-POTENTIALS
CA2+ CHANNELS
RIBBON SIZE
GUINEA-PIG
COCHLEAR
HEARING
CURRENTS
期刊
IF:
0
论文数:
1.8W
被引数:
16
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RSC AdvancesOAAI
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OAAI分享收藏RIBEYE, a component of synaptic ribbons:: A protein's journey through evolution provides insight into synaptic ribbon functionNEURON
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NEURONIF15
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