Hussain Saman, Pinter Katherine, Uhl Mara, Wong Hiu-Tung, Kindt Katie S
Section on Sensory Cell Development and Function, National Institute on Deafness and other Communication Disorders, Bethesda, United States.
Presynaptogenesis and Intracellular Transport in Hair Cells Junior Research Group, Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Goettingen, Goettingen, Germany.
Elife. 2025 Jul 23;13:RP98119. doi: 10.7554/eLife.98119.
Sensory cells in the retina and inner ear rely on specialized ribbon synapses for neurotransmission. Disruption of these synapses is linked to visual and auditory dysfunction, but it is unclear how these unique synapses form. Ribbon synapses are defined by a presynaptic density called a ribbon. Using live imaging in zebrafish hair cells, we find that numerous small ribbon precursors are present throughout the cell early in development. As development progresses, fewer large ribbons remain, and localize at the presynaptic active zone (AZ). Using tracking analyses, we show that ribbon precursors exhibit directed motion along an organized microtubule network to reach the presynaptic AZ. In addition, we show that ribbon precursors can fuse together on microtubules. Using pharmacology, we find that microtubule disruption interferes with ribbon motion, fusion, and normal synapse formation. Overall, this work demonstrates a dynamic series of events that underlies the formation of a critical synapse required for sensory function.
视网膜和内耳中的感觉细胞依靠特殊的带状突触进行神经传递。这些突触的破坏与视觉和听觉功能障碍有关,但目前尚不清楚这些独特的突触是如何形成的。带状突触由一种称为突触带的突触前致密物所定义。通过对斑马鱼毛细胞进行实时成像,我们发现在发育早期,细胞内存在大量小的突触带前体。随着发育的进行,剩余的大突触带数量减少,并定位于突触前活性区(AZ)。通过追踪分析,我们表明突触带前体沿着有组织的微管网络进行定向运动,以到达突触前活性区。此外,我们还表明突触带前体可以在微管上融合在一起。通过药理学方法,我们发现微管破坏会干扰突触带的运动、融合以及正常突触的形成。总体而言,这项工作展示了一系列动态事件,这些事件是感觉功能所需关键突触形成的基础。