PDF(Pubmed)
Abstract：
Adaptation of photoreceptor sensitivity to varying light intensities is a fundamental requirement for retinal function and vision. Adaptive mechanisms in signal transduction are well described, but little is known about the mechanisms that adapt the photoreceptor synapse to changing light intensities. The SNARE complex regulators Complexin 3 and Complexin 4 have been proposed to be involved in synaptic light adaptation by limiting synaptic vesicle recruitment and fusion. How this Complexin effect is exerted is unknown. Focusing on rod photoreceptors, we established Complexin 4 as the predominant Complexin in the light-dependent regulation of neurotransmitter release. The number of readily releasable synaptic vesicles is significantly smaller in light than in dark at wildtype compared to Complexin 4 deficient rod photoreceptor ribbon synapses. Electrophysiology indicates that Complexin 4 reduces or clamps Ca2+-dependent sustained synaptic vesicle release, thereby enhancing light signaling at the synapse. Complexin 4 deficiency increased synaptic vesicle release and desensitized light signaling. In a quantitative proteomic screen, we identified Transducin as an interactor of the Complexin 4-SNARE complex. Our results provide evidence for a presynaptic interplay of both Complexin 4 and Transducin with the SNARE complex, an interplay that may facilitate the adaptation of synaptic transmission to light at rod photoreceptor ribbon synapses.
摘要：
使光感受器灵敏度适应变化的光强度是视网膜功能和视力的基本要求。信号转导中的适应性机制已得到很好的描述，但是对使光感受器突触适应变化的光强度的机制知之甚少。已经提出SNARE复合物调节剂Complexin3和Complexin4通过限制突触小泡募集和融合而参与突触光适应。如何发挥这种Complexin效应是未知的。专注于杆状光感受器，我们将Complexin4确定为神经递质释放的光依赖性调节中的主要Complexin。与缺乏Complexin4的杆状光感受器带状突触相比，在野生型下，在光照下容易释放的突触小泡的数量明显少于黑暗。电生理学表明Complexin4减少或抑制Ca2+依赖的持续突触小泡释放，从而增强突触处的光信号。配合素4缺乏增加了突触小泡释放和光信号脱敏。在定量蛋白质组学筛选中，我们确定Transducin是Complexin4-SNARE复合物的相互作用者。我们的结果为Complexin4和Transducin与SNARE复合物的突触前相互作用提供了证据，可以促进突触传递对光在视杆感光带突触处的适应的相互作用。
