Godenschwege Tanja A, Hu Hailan, Shan-Crofts Xiaoliang, Goodman Corey S, Murphey Rodney K
University of Massachusetts, Department of Biology, Morrill Science Center, Amherst, Massachusetts 01003, USA.
Nat Neurosci. 2002 Dec;5(12):1294-301. doi: 10.1038/nn976.
Semaphorins have been intensively studied for their role in dendritic and axonal pathfinding, but less is known about their potential role in synapse formation. In the adult giant fiber (GF) system of fruit flies (Drosophila melanogaster), we show that transmembrane Semaphorin 1a (Sema-1a) is involved in synapse formation in addition to its role in guidance during pathfinding. Cell-autonomous rescue experiments showed that Sema-1a is involved in assembly of a central synapse and that it is required both pre- and postsynaptically. We also found that pre- but not postsynaptic gain-of-function Sema-1a was able to disrupt the GF-motor neuron synapse and that the phenotype depended on a proline-rich intracellular domain that contains a putative Enabled binding site. We suggest that transmembrane Sema-1a is part of a bi-directional signaling system that leads to the formation of the GF synapse and possibly acts as both a ligand and a receptor.
信号素在树突和轴突路径寻找中的作用已得到深入研究，但它们在突触形成中的潜在作用却鲜为人知。在果蝇（黑腹果蝇）的成年巨纤维（GF）系统中，我们发现跨膜信号素1a（Sema-1a）除了在路径寻找过程中的导向作用外，还参与突触形成。细胞自主拯救实验表明，Sema-1a参与中央突触的组装，并且在突触前和突触后都需要它。我们还发现，突触前功能获得性的Sema-1a能够破坏GF-运动神经元突触，但突触后功能获得性的Sema-1a则不能，并且该表型取决于一个富含脯氨酸的细胞内结构域，该结构域包含一个假定的Enabled结合位点。我们认为跨膜Sema-1a是双向信号系统的一部分，该系统导致GF突触的形成，并且可能同时作为配体和受体发挥作用。
