Suiwal Shweta, Schwarz Karin, Maxeiner Stephan, Schmitz Frank
Institute of Anatomy and Cell Biology, Medical School Homburg, Saarland University, 66421 Homburg, Germany.
Int J Mol Sci. 2025 Jun 24;26(13):6044. doi: 10.3390/ijms26136044.
Retinal ribbon synapses are continuously active chemical synapses. The eponymous synaptic ribbon is anchored to the active zone neurotransmitter release sites of ribbon synapses, recruits synaptic vesicles and guides ribbon-associated synaptic vesicles to the release sites. RIBEYE is the major protein component of synaptic ribbons. But likely, additional proteins contribute to ribbon synapse function. The synaptic ribbon of photoreceptor synapses is embedded into a highly polarized microtubule cytoskeleton. Interestingly, proteins of the photoreceptor primary cilium, such as NPHP4 and other ciliary proteins, including KIF3A, were shown to be localized to photoreceptor synaptic ribbons. Previous studies demonstrated that the microtubule motor protein KIF13B catalyzes secretory vesicle transport to the plus ends of microtubules and identified an interaction of KIF13B with NPHP4 at primary cilia. However, the localization of KIF13B, a kinesin-3 family motor protein, in the retina is still unknown. In the present study, we used two different antibodies against KIF13B and high-resolution confocal microscopy, super-resolution structured illumination microscopy (SR-SIM), and post-embedding immunogold electron microscopy to determine the localization of KIF13B in retinal photoreceptors. Apart from its localization at the primary photoreceptor cilium, we found a strong enrichment of KIF13B at photoreceptor synaptic ribbons. The synaptic ribbon is needed for the synaptic enrichment of KIF13B as shown by analyses of synaptic ribbon-deficient RIBEYE knockout mice. These findings suggest that KIF13B performs vesicle trafficking functions at the photoreceptor synaptic ribbon complex at the interface between the synaptic ribbon and the presynaptic microtubule transport system.
视网膜带状突触是持续活跃的化学突触。同名的突触带锚定在带状突触的活性区神经递质释放位点，募集突触小泡并引导与突触带相关的突触小泡至释放位点。RIBEYE是突触带的主要蛋白质成分。但可能还有其他蛋白质对带状突触功能有贡献。光感受器突触的突触带嵌入高度极化的微管细胞骨架中。有趣的是，光感受器初级纤毛的蛋白质，如NPHP4和其他纤毛蛋白，包括KIF3A，被证明定位于光感受器突触带。先前的研究表明，微管运动蛋白KIF13B催化分泌小泡向微管正端的运输，并确定了KIF13B与初级纤毛处的NPHP4之间的相互作用。然而，驱动蛋白-3家族运动蛋白KIF13B在视网膜中的定位仍不清楚。在本研究中，我们使用两种针对KIF13B的不同抗体以及高分辨率共聚焦显微镜、超分辨率结构光照显微镜（SR-SIM）和包埋后免疫金电子显微镜来确定KIF13B在视网膜光感受器中的定位。除了定位于光感受器初级纤毛外，我们还发现KIF13B在光感受器突触带中大量富集。对缺乏突触带的RIBEYE基因敲除小鼠的分析表明，突触带是KIF13B在突触处富集所必需的。这些发现表明，KIF13B在突触带与突触前微管运输系统之间界面处的光感受器突触带复合体上执行囊泡运输功能。
