Toll-6 and Toll-7 function as neurotrophin receptors in the Drosophila melanogaster CNS.
Toll-6 and Toll-7 function as neurotrophin receptors in the Drosophila melanogaster CNS.
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Toll-6和TOLL-7在果蝇Melanogaster CNS中充当神经营养蛋白受体。
DOI：
10.1038/nn.3474
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发表时间：
2013-09
影响因子：
25
通讯作者：
Hidalgo A
中科院分区：
文献类型：
--
作者：
McIlroy G;Foldi I;Aurikko J;Wentzell JS;Lim MA;Fenton JC;Gay NJ;Hidalgo A
果蝇中尚未鉴定出对应于脊椎动物 Trk、p75NTR 或 Sortilin 的神经营养蛋白受体，因此尚不清楚昆虫中如何实现神经营养作用。两种果蝇神经营养蛋白 DNT1 和 DNT2 具有神经系统功能，但它们的受体尚不清楚。 Toll 受体超家族具有古老的进化起源和先天免疫中的普遍功能。在这里，我们证明与哺乳动物神经营养蛋白受体无关的 Toll 旁系同源物在果蝇中充当神经营养蛋白受体。 Toll-6 和 Toll-7 在整个发育过程中在中枢神经系统中表达，并调节运动、运动轴突靶向和神经元存活。 DNT1 和 2 与 Toll-6 和 7 发生遗传相互作用，与 Toll-7 和 6 混杂结合，并在体内分布在互补或重叠的结构域中。我们得出的结论是，在果蝇中，Tolls 不仅参与发育和免疫，还参与神经营养作用，揭示了神经营养蛋白和 Toll 蛋白家族之间不可预见的关系。
Neurotrophin receptors corresponding to vertebrate Trk, p75NTR or Sortilin have not been identified in Drosophila, thus it is unknown how neurotrophism may be implemented in insects. Two Drosophila neurotrophins, DNT1 and DNT2, have nervous system functions, but their receptors are unknown. The Toll receptor superfamily has ancient evolutionary origins and a universal function in innate immunity. Here we show that Toll paralogues unrelated to the mammalian neurotrophin receptors function as neurotrophin receptors in fruit-flies. Toll-6 and Toll-7 are expressed in the central nervous system throughout development, and regulate locomotion, motoraxon targeting and neuronal survival. DNT1 and 2 interact genetically with Toll-6 and 7, bind to Toll-7 and 6 promiscuously, and are distributed in vivo in complementary or overlapping domains. We conclude that in fruit-flies, Tolls are not only involved in development and immunity but also in neurotrophism, revealing an unforeseen relationship between the neurotrophin and Toll protein families.