PDF(Pubmed)
Abstract：
Sensory hair cells of the inner ear utilize specialized ribbon synapses to transmit sensory stimuli to the central nervous system. This sensory transmission necessitates rapid and sustained neurotransmitter release, which relies on a large pool of synaptic vesicles at the hair-cell presynapse. Work in neurons has shown that kinesin motor proteins traffic synaptic material along microtubules to the presynapse, but how new synaptic material reaches the presynapse in hair cells is not known. We show that the kinesin motor protein Kif1a and an intact microtubule network are necessary to enrich synaptic vesicles at the presynapse in hair cells. We use genetics and pharmacology to disrupt Kif1a function and impair microtubule networks in hair cells of the zebrafish lateral-line system. We find that these manipulations decrease synaptic-vesicle populations at the presynapse in hair cells. Using electron microscopy, along with in vivo calcium imaging and electrophysiology, we show that a diminished supply of synaptic vesicles adversely affects ribbon-synapse function. Kif1a mutants exhibit dramatic reductions in spontaneous vesicle release and evoked postsynaptic calcium responses. Additionally, we find that kif1a mutants exhibit impaired rheotaxis, a behavior reliant on the ability of hair cells in the lateral line to respond to sustained flow stimuli. Overall, our results demonstrate that Kif1a-based microtubule transport is critical to enrich synaptic vesicles at the active zone in hair cells, a process that is vital for proper ribbon-synapse function.
摘要：
内耳的感觉毛细胞利用专门的带状突触将感觉刺激传递到中枢神经系统。这种感觉传递需要快速和持续的神经递质释放，它依赖于毛细胞突触前的大量突触小泡。在神经元中的工作表明，驱动蛋白运动蛋白沿着微管将突触物质运送到突触前，但是新的突触物质如何到达毛细胞的突触前还不清楚。我们表明，驱动蛋白运动蛋白Kif1a和完整的微管网络对于富集毛细胞突触前的突触小泡是必需的。我们使用遗传学和药理学来破坏Kif1a功能并损害斑马鱼侧线系统毛细胞中的微管网络。我们发现这些操作减少了毛细胞突触前的突触-囊泡种群。使用电子显微镜，随着体内钙成像和电生理学，我们表明，突触小泡的供应减少会对带状突触功能产生不利影响。Kif1a突变体表现出自发囊泡释放和诱发的突触后钙反应的显着减少。此外,我们发现kif1a突变体表现出受损的流变倾向，一种依赖于侧线毛细胞对持续流动刺激的反应能力的行为。总的来说,我们的结果表明，基于Kif1a的微管运输是至关重要的，以丰富的突触小泡在毛细胞的活动区，一个对正常的带状突触功能至关重要的过程。
■Kif1amRNA存在于斑马鱼毛细胞中Kif1a的缺失会破坏带状突触中突触小泡的富集微管的破坏会耗尽带状突触中的突触小泡Kif1a突变体的带状突触和感觉系统功能受损。
■Kif1amRNA存在于斑马鱼毛细胞中Kif1a的缺失会破坏带状突触中突触小泡的富集微管的破坏会耗尽带状突触中的突触小泡Kif1a突变体的带状突触和感觉系统功能受损。
