Three Drosophila liprins interact to control synapse formation.
Three Drosophila liprins interact to control synapse formation.
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DOI：
10.1523/jneurosci.1862-10.2010
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发表时间：
2010-11-17
期刊：
影响因子：
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通讯作者：
Treisman JE
中科院分区：
文献类型：
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作者：
Astigarraga S;Hofmeyer K;Farajian R;Treisman JE
Liprin-α蛋白是与受体蛋白酪氨酸磷酸酶LAR和其他突触蛋白相互作用以促进突触伴侣选择和活性区组装的衔接子。Liprin-β蛋白与Liprin-α蛋白结合并具有同源性，但它们在突触中的功能尚不清楚。果蝇基因组编码单个Liprin-α和Liprin-β同系物，以及我们命名为Liprin-γ的第三种相关蛋白。我们发现Liprin-β和Liprin-γ都与Liprin-α发生物理相互作用，Liprin-γ也与LAR结合。Liprin-α突变已被证明会破坏R7光感受器对突触靶层的选择，并减少幼虫神经肌肉突触的大小。我们已经在Liprin-β和Liprin-γ中产生了无效突变，以研究它们在这些过程中的作用。我们发现，虽然Liprin-α突变体R7轴突在到达正确的靶层之前终止，但Liprin-β突变体R7轴突生长超过其靶层。在Liprin-α和Liprinβ突变体中，幼虫神经肌肉接头的大小都减小，并且在双突变体中进一步减小，表明这些Liprin具有独立的功能。遗传相互作用表明，这两种Liprin蛋白通过交换因子Trio发挥作用，以促进R7光感受器轴突的稳定靶选择和神经肌肉突触的生长。光感受器和神经肌肉突触在Liprin-γ突变体中正常发育;然而，去除Liprin-γ改善了Liprin-α突变体中的R7靶向，并恢复了Liprin-β突变体的正常神经肌肉接头大小，表明Liprin-γ抵消了其他两种Liprin的功能。我们建议，上下文依赖的相互作用之间的三个Liprins调节它们的功能，突触的形成。
Liprin-α proteins are adaptors that interact with the receptor protein tyrosine phosphatase LAR and other synaptic proteins to promote synaptic partner selection and active zone assembly. Liprin-β proteins bind to and share homology with Liprin-α proteins, but their functions at the synapse are unknown. The Drosophila genome encodes single Liprin-α and Liprin-β homologues, as well as a third related protein that we named Liprin-γ. We show that both Liprin-β and Liprin-γ physically interact with Liprin-α, and that Liprin-γ also binds to LAR. Liprin-α mutations have been shown to disrupt synaptic target layer selection by R7 photoreceptors and to reduce the size of larval neuromuscular synapses. We have generated null mutations in Liprin-β and Liprin-γ to investigate their role in these processes. We find that while Liprin-α mutant R7 axons terminate before reaching the correct target layer, Liprin-β mutant R7 axons grow beyond their target layer. Larval neuromuscular junction size is reduced in both Liprin-α and Liprinβ-mutants, and further reduced in double mutants, suggesting independent functions for these Liprins. Genetic interactions demonstrate that both Liprin proteins act through the exchange factor Trio to promote stable target selection by R7 photoreceptor axons and growth of neuromuscular synapses. Photoreceptor and neuromuscular synapses develop normally in Liprin-γ mutants; however, removing Liprin-γ improves R7 targeting in Liprin-α mutants, and restores normal neuromuscular junction size to Liprin-β mutants, suggesting that Liprin-γ counteracts the functions of the other two Liprins. We propose that context-dependent interactions between the three Liprins modulate their functions in synapse formation.