Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Dev Cell. 2014 Dec 8;31(5):586-98. doi: 10.1016/j.devcel.2014.10.006. Epub 2014 Nov 20.
Distinct pools of the bone morphogenetic protein (BMP) Glass bottom boat (Gbb) control structure and function of the Drosophila neuromuscular junction. Specifically, motoneuron-derived Gbb regulates baseline neurotransmitter release, whereas muscle-derived Gbb regulates neuromuscular junction growth. Yet how cells differentiate between these ligand pools is not known. Here we present evidence that the neuronal Gbb-binding protein Crimpy (Cmpy) permits discrimination of pre- and postsynaptic ligand by serving sequential functions in Gbb signaling. Cmpy first delivers Gbb to dense core vesicles (DCVs) for activity-dependent release from presynaptic terminals. In the absence of Cmpy, Gbb is no longer associated with DCVs and is not released by activity. Electrophysiological analyses demonstrate that Cmpy promotes Gbb's proneurotransmission function. Surprisingly, the Cmpy ectodomain is itself released upon DCV exocytosis, arguing that Cmpy serves a second function in BMP signaling. In addition to trafficking Gbb to DCVs, we propose that Gbb/Cmpy corelease from presynaptic terminals defines a neuronal protransmission signal.
骨形态发生蛋白（BMP） Glass bottom boat（Gbb）的不同池控制果蝇神经肌肉接头的结构和功能。具体来说，运动神经元衍生的 Gbb 调节基线神经递质释放，而肌肉衍生的 Gbb 调节神经肌肉接头生长。然而，细胞如何区分这些配体池尚不清楚。在这里，我们提供的证据表明，神经元 Gbb 结合蛋白 Crimpy（Cmpy）通过在 Gbb 信号传递中发挥连续功能来区分突触前和突触后配体。Cmpy 首先将 Gbb 递送至致密核心囊泡（DCVs），以供从突触前末端进行活性依赖性释放。在没有 Cmpy 的情况下，Gbb 不再与 DCVs 相关联，并且不会被活性释放。电生理分析表明 Cmpy 促进 Gbb 的神经传递功能。令人惊讶的是，Cmpy 的细胞外结构域本身在 DCV 胞吐作用时被释放，这表明 Cmpy 在 BMP 信号传递中具有第二个功能。除了将 Gbb 转运到 DCVs 之外，我们还提出 Gbb/Cmpy 从突触前末端的共释放定义了神经元的神经传递信号。
