Department of Genetics, Institute for Biology, Freie Universität Berlin, 14195 Berlin, Germany.
J Cell Biol. 2010 Feb 22;188(4):565-79. doi: 10.1083/jcb.200908055.
Active zones (AZs) are presynaptic membrane domains mediating synaptic vesicle fusion opposite postsynaptic densities (PSDs). At the Drosophila neuromuscular junction, the ELKS family member Bruchpilot (BRP) is essential for dense body formation and functional maturation of AZs. Using a proteomics approach, we identified Drosophila Syd-1 (DSyd-1) as a BRP binding partner. In vivo imaging shows that DSyd-1 arrives early at nascent AZs together with DLiprin-alpha, and both proteins localize to the AZ edge as the AZ matures. Mutants in dsyd-1 form smaller terminals with fewer release sites, and release less neurotransmitter. The remaining AZs are often large and misshapen, and ectopic, electron-dense accumulations of BRP form in boutons and axons. Furthermore, glutamate receptor content at PSDs increases because of excessive DGluRIIA accumulation. The AZ protein DSyd-1 is needed to properly localize DLiprin-alpha at AZs, and seems to control effective nucleation of newly forming AZs together with DLiprin-alpha. DSyd-1 also organizes trans-synaptic signaling to control maturation of PSD composition independently of DLiprin-alpha.
活性区 (AZs) 是介导突触小泡融合在突触后密度 (PSDs) 对面的突触前膜域。在果蝇神经肌肉接头中，ELKS 家族成员 Bruchpilot (BRP) 对于致密体的形成和 AZs 的功能成熟是必不可少的。使用蛋白质组学方法，我们鉴定出果蝇 Syd-1 (DSyd-1) 是 BRP 的结合伴侣。体内成像显示，DSyd-1 与 DLiprin-alpha 一起早期到达新生的 AZs，并且这两种蛋白在 AZ 成熟时定位于 AZ 边缘。dsyd-1 突变体形成的末端较小，释放位点较少，释放的神经递质较少。剩余的 AZs 通常较大且畸形，BRP 的异位、电子致密积累形成在末梢和轴突中。此外，由于 DGluRIIA 过度积累，PSD 处的谷氨酸受体含量增加。AZ 蛋白 DSyd-1 对于 DLiprin-alpha 在 AZs 上的正确定位是必需的，并且似乎与 DLiprin-alpha 一起控制新形成的 AZs 的有效成核。DSyd-1 还组织跨突触信号传递，独立于 DLiprin-alpha 控制 PSD 组成的成熟。
