脊椎动物的视觉始于杆状和锥形光感受器的光吸收,将信号从其突触末端传输到二阶神经元:双极和水平细胞。在鼠标杆中,有一个单一的突触前带状活动区,在黑暗中,谷氨酸的释放发生。这种强直的谷氨酸能信号需要突触囊泡的连续胞外和内吞作用。在传统的突触中,内吞作用通常需要动力蛋白:由三个基因编码的GTP酶(Dnm1-3),进行膜断裂。通过动态蛋白缺失破坏内吞作用会损害常规突触的传递,但是,破坏胞吞作用的影响以及杆带突触中特定动力学蛋白同工型的作用尚未完全理解。这里,我们使用神经元特异性Dnm1和Dnm3的细胞特异性敲除来研究动力蛋白同工型在两种性别的小鼠杆状光感受器中的功能作用。突触蛋白表达分析,突触超微结构,和视网膜功能通过视网膜电图显示,动力蛋白1和3冗余地起作用,对于支持棒带突触的结构和功能完整性至关重要。单个Dnm3敲除显示无表型,单个Dnm1敲除仅适度降低突触小泡密度,而不影响小泡大小和整体突触完整性;双重Dnm1/Dnm3敲除严重损害囊泡内吞作用,导致囊泡增大,囊泡密度降低,减少ERG响应,突触终末变性,以及突触后过程的分解和退化。同时,锥功能保持不变。这些结果表明,动态蛋白1和3在调节棒带突触的结构和功能方面具有基本的冗余。意义陈述视觉过程始于视网膜内的视杆和视锥光感受器捕获光。光感受器在称为带状突触的特殊部位与下游视网膜神经元通信,神经递质谷氨酸的囊泡被释放和回收。常规突触的突触小泡循环过程通常需要特殊的蛋白质来进行膜断裂,通常是动态1和3。动力蛋白在感光带突触的囊泡循环中的作用,然而,没有完全理解。这里,我们使用条件基因敲除方法特异性地删除了杆状光感受器中的动力蛋白1和3,并证明了动力蛋白1和3在维持杆状光感受器带状突触结构和功能方面的冗余作用。
Vertebrate vision begins with light absorption by rod and cone photoreceptors, which transmit signals from their synaptic terminals to second-order neurons: bipolar and horizontal cells. In mouse rods, there is a single presynaptic ribbon-type active zone at which the release of glutamate occurs tonically in the dark. This tonic glutamatergic signaling requires continuous exo- and endocytosis of synaptic vesicles. At conventional synapses, endocytosis commonly requires dynamins: GTPases encoded by three genes (Dnm1-3), which perform membrane scission. Disrupting endocytosis by dynamin deletions impairs transmission at conventional synapses, but the impact of disrupting endocytosis and the role(s) of specific dynamin isoforms at rod ribbon synapses are understood incompletely. Here, we used cell-specific knock-outs (KOs) of the neuron-specific Dnm1 and Dnm3 to investigate the functional roles of dynamin isoforms in rod photoreceptors in mice of either sex. Analysis of synaptic protein expression, synapse ultrastructure, and retinal function via electroretinograms (ERGs) showed that dynamins 1 and 3 act redundantly and are essential for supporting the structural and functional integrity of rod ribbon synapses. Single Dnm3 KO showed no phenotype, and single Dnm1 KO only modestly reduced synaptic vesicle density without affecting vesicle size and overall synapse integrity, whereas double Dnm1/Dnm3 KO impaired vesicle endocytosis profoundly, causing enlarged vesicles, reduced vesicle density, reduced ERG responses, synaptic terminal degeneration, and disassembly and degeneration of postsynaptic processes. Concurrently, cone function remained intact. These results show the fundamental redundancy of dynamins 1 and 3 in regulating the structure and function of rod ribbon synapses.