Bi-directional signaling by Semaphorin 1a during central synapse formation in Drosophila

Bi-directional signaling by Semaphorin 1a during central synapse formation in Drosophila
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DOI:
10.1038/nn976
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发表时间:
2002-12-01
影响因子:
25
通讯作者:
Murphey, RK
Murphey, RK
中科院分区:
医学1区
文献类型:
--
作者:
Godenschwege, TA;Hu, HL;Murphey, RK

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信号素在树突状细胞和轴突通路中的作用已被广泛研究,但对其在突触形成中的潜在作用知之甚少。在果蝇的成虫巨纤维(GF)系统中,我们发现跨膜信号素1a(SEMA-1a)除了在寻路过程中起指导作用外,还参与突触的形成。细胞自主抢救实验表明,Sema-1a参与了中央突触的组装,突触前和突触后都需要它。我们还发现,突触前而不是突触后的功能获得-Sema-1a能够破坏GF运动神经元的突触,并且其表型依赖于一个富含Pro的胞内结构域,该结构域包含一个假定的使能结合部位。我们认为跨膜Sema-1a是导致GF突触形成的双向信号系统的一部分,可能既是配体又是受体。
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-la 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.