Aberrant function and structure of retinal ribbon synapses in the absence of complexin 3 and complexin 4
Aberrant function and structure of retinal ribbon synapses in the absence of complexin 3 and complexin 4
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DOI：
10.1242/jcs.045401
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发表时间：
2009-05-01
影响因子：
4
通讯作者：
Brose, Nils
中科院分区：
文献类型：
--
作者：
Reim, Kerstin;Regus-Leidig, Hanna;Brose, Nils
复合蛋白调节SNARE介导的突触囊泡融合在常规突触中的速度和Ca 2+敏感性。脊椎动物复合蛋白中的两种，Cplx3和Cplx4，特异性地定位于视网膜带状突触。为了测试Cplx3和Cplx4是否有助于带状突触处的高效递质释放，我们研究了Cplx3和Cplx4单敲除和双敲除小鼠的视网膜功能和结构。视网膜电图记录从单，双突变体显示合作干扰效果的Cplx3和Cplx4删除的b波振幅，而大多数其他检测到的效果在两个丛状突触层是加性的。光学和电子显微镜分析发现，缺乏Cplx 3和Cplx 4的小鼠视网膜中存在杂乱无章的外丛状层，其中很大一部分光感受器末端含有球形自由浮动的丝带。这些结构和功能异常伴随着行为缺陷，表明视力缺陷。我们的研究结果表明，Cplx3和Cplx4是视网膜带状突触递质释放的重要调节因子。它们的丢失导致感光带突触的递质释放的异常调节和微调，双极细胞末端的传递改变，视网膜内丛状层突触处理的时间结构改变和视觉干扰。
Complexins regulate the speed and Ca2+ sensitivity of SNARE-mediated synaptic vesicle fusion at conventional synapses. Two of the vertebrate complexins, Cplx3 and Cplx4, are specifically localized to retinal ribbon synapses. To test whether Cplx3 and Cplx4 contribute to the highly efficient transmitter release at ribbon synapses, we studied retina function and structure in Cplx3 and Cplx4 single- and double-knockout mice. Electroretinographic recordings from single and double mutants revealed a cooperative perturbing effect of Cplx3 and Cplx4 deletion on the b-wave amplitude, whereas most other detected effects in both plexiform synaptic layers were additive. Light and electron microscopic analyses uncovered a disorganized outer plexiform layer in the retinae of mice lacking Cplx3 and Cplx4, with a significant proportion of photoreceptor terminals containing spherical free-floating ribbons. These structural and functional aberrations were accompanied by behavioural deficits indicative of a vision deficit. Our results show that Cplx3 and Cplx4 are essential regulators of transmitter release at retinal ribbon synapses. Their loss leads to aberrant adjustment and fine-tuning of transmitter release at the photoreceptor ribbon synapse, alterations in transmission at bipolar cell terminals, changes in the temporal structure of synaptic processing in the inner plexiform layer of the retina and perturbed vision.