Department of Developmental Biology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
Neuron. 2009 Dec 10;64(5):663-77. doi: 10.1016/j.neuron.2009.11.002.
Synaptic transmission requires the localization of presynaptic release machinery to active zones. Mechanisms regulating the abundance of such synaptic proteins at individual release sites are likely determinants of site-specific synaptic efficacy. We now identify a role for the small GTPase Rab3 in regulating the distribution of presynaptic components to active zones. At Drosophila rab3 mutant NMJs, the presynaptic protein Bruchpilot, calcium channels, and electron-dense T bars are concentrated at a fraction of available active zones, leaving the majority of sites devoid of these key presynaptic release components. Late addition of Rab3 to mutant NMJs rapidly reverses this phenotype by recruiting Brp to sites previously lacking the protein, demonstrating that Rab3 can dynamically control the composition of the presynaptic release machinery. While previous studies of Rab3 have focused on its role in the synaptic vesicle cycle, these findings demonstrate an additional and unexpected function for Rab3 in the localization of presynaptic proteins to active zones.
突触传递需要将突触前释放机制定位到活性区。调节单个释放位点中这种突触蛋白丰度的机制可能是决定特定突触效能的因素。我们现在确定了小 GTPase Rab3 在调节突触前成分向活性区分布中的作用。在果蝇 rab3 突变 NMJs 中，突触前蛋白 Bruchpilot、钙通道和电子致密 T 棒集中在可用活性区的一小部分，而大部分位点缺乏这些关键的突触前释放成分。将 Rab3 晚期添加到突变 NMJs 中，可以通过将 Brp 募集到以前缺乏该蛋白的部位来快速逆转这种表型，表明 Rab3 可以动态控制突触前释放机制的组成。虽然之前对 Rab3 的研究集中在其在突触小泡循环中的作用，但这些发现表明 Rab3 在将突触前蛋白定位到活性区方面具有额外的、意想不到的功能。
