Munc13-Independent Vesicle Priming at Mouse Photoreceptor Ribbon Synapses
Munc13-Independent Vesicle Priming at Mouse Photoreceptor Ribbon Synapses
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DOI：
10.1523/jneurosci.4240-11.2012
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发表时间：
2012-06-06
影响因子：
5.3
通讯作者：
Varoqueaux, Frederique
中科院分区：
文献类型：
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作者：
Cooper, Benjamin;Hemmerlein, Maike;Varoqueaux, Frederique
Munc13蛋白是胞吐作用的重要调节因子。在海马谷氨酸能神经元中，Munc13s基因缺失导致与突触前活性区膜直接接触的预适应突触小泡(SVS)完全丧失，神经递质释放完全受阻。同样，Munc13缺失的严重后果也可以在海马区和纹状体的GABA能神经元中检测到。我们发现，在成年小鼠视网膜中，两个Munc13-2剪接变异体bMunc13-2和ubMunc13-2分别选择性地定位于常规突触和带状突触，并且ubMunc13-2是成熟光感受器带状突触中唯一的Munc13亚型。值得注意的是，ubMunc13-2基因的缺失对感光带突触传递的信号影响不大，也不能阻止突触囊泡在感光带突触部位的膜附着。因此，光感受器带状突触和常规突触在依赖Munc13家族的SV启动蛋白方面有根本的不同。它们的功能只会受到Munc13丢失的适度影响，这会导致视网膜信号整合的轻微干扰。
Munc13 proteins are essential regulators of exocytosis. In hippocampal glutamatergic neurons, the genetic deletion of Munc13s results in the complete loss of primed synaptic vesicles (SVs) in direct contact with the presynaptic active zone membrane, and in a total block of neurotransmitter release. Similarly drastic consequences of Munc13 loss are detectable in hippocampal and striatal GABAergic neurons. We show here that, in the adult mouse retina, the two Munc13-2 splice variants bMunc13-2 and ubMunc13-2 are selectively localized to conventional and ribbon synapses, respectively, and that ubMunc13-2 is the only Munc13 isoform in mature photoreceptor ribbon synapses. Strikingly, the genetic deletion of ubMunc13-2 has little effect on synaptic signaling by photoreceptor ribbon synapses and does not prevent membrane attachment of synaptic vesicles at the photoreceptor ribbon synaptic site. Thus, photoreceptor ribbon synapses and conventional synapses differ fundamentally with regard to their dependence on SV priming proteins of the Munc13 family. Their function is only moderately affected by Munc13 loss, which leads to slight perturbations of signal integration in the retina.