RIM promotes calcium channel accumulation at active zones of the Drosophila neuromuscular junction.
RIM promotes calcium channel accumulation at active zones of the Drosophila neuromuscular junction.
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RIM 促进果蝇神经肌肉接头活跃区的钙通道积累
DOI：
10.1523/jneurosci.0965-12.2012
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发表时间：
2012-11-21
期刊：
影响因子：
--
通讯作者：
DiAntonio A
中科院分区：
文献类型：
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作者：
Graf ER;Valakh V;Wright CM;Wu C;Liu Z;Zhang YQ;DiAntonio A
突触通讯需要突触前轴突终末突触囊泡的受控释放。释放效能由包括突触前释放装置的许多蛋白质调节，包括Ca 2+通道和影响Ca 2+通道在释放位点积聚的蛋白质。在这里，我们确定果蝇RIM（Rab3相互作用分子），并证明它定位于幼虫神经肌肉接头的活动区。在果蝇RIM突变体，有一个很大的减少诱发突触传递，因为一个显着的减少，在两个集群的Ca 2+通道和大小的突触囊泡在活动区容易释放池。因此，RIM在调节突触钙通道定位和易于释放的池大小方面起着进化上保守的作用。由于RIM传统上已被研究Rab3功能的效应器，我们调查RIM是否参与了新发现的Rab3在突触前释放机制组件的分布在整个释放位点的功能。Bruchpilot（Brp）是活性区细胞基质T条的重要组成部分，不受RIM破坏的影响，表明Brp在活性区的定位和分布不需要野生型RIM。此外，RIM和rab 3均含有突变的幼虫的Ca 2+通道水平降低，Brp分布与rab 3单一突变体非常相似，这表明RIM的功能是调节Ca 2+通道积累，但不是Rab 3效应子。释放机制分布在释放位点。
Synaptic communication requires the controlled release of synaptic vesicles from presynaptic axon terminals. Release efficacy is regulated by the many proteins that comprise the presynaptic release apparatus, including Ca2+ channels and proteins that influence Ca2+ channel accumulation at release sites. Here we identify Drosophila RIM (Rab3 interacting molecule) and demonstrate that it localizes to active zones at the larval neuromuscular junction. In Drosophila RIM mutants, there is a large decrease in evoked synaptic transmission because of a significant reduction in both the clustering of Ca2+ channels and the size of the readily releasable pool of synaptic vesicles at active zones. Hence, RIM plays an evolutionarily conserved role in regulating synaptic calcium channel localization and readily releasable pool size. Because RIM has traditionally been studied as an effector of Rab3 function, we investigate whether RIM is involved in the newly identified function of Rab3 in the distribution of presynaptic release machinery components across release sites. Bruchpilot (Brp), an essential component of the active zone cytomatrix T bar, is unaffected by RIM disruption, indicating that Brp localization and distribution across active zones does not require wild-type RIM. In addition, larvae containing mutations in both RIM and rab3 have reduced Ca2+ channel levels and a Brp distribution that is very similar to that of the rab3 single mutant, indicating that RIM functions to regulate Ca2+ channel accumulation but is not a Rab3 effector for release machinery distribution across release sites.