Characterization of Spz5 as a novel ligand for Drosophila Toll-1 receptor
Characterization of Spz5 as a novel ligand for Drosophila Toll-1 receptor
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DOI：
10.1016/j.bbrc.2018.10.096
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发表时间：
2018-11-30
影响因子：
3.1
通讯作者：
Kuraishi, Takayuki
中科院分区：
文献类型：
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作者：
Nonaka, Saori;Kawamura, Koichiro;Kuraishi, Takayuki
果蝇Toll-1受体参与胚胎发育、先天免疫和组织稳态。目前，作为Toll-1受体的配体，只有Spatzle（Spz）已被鉴定和表征。我们以前曾报道，果蝇幼虫衍生的组织提取物含有Toll-1受体的配体活性，这不同于SPZ的基础上观察，从SPZ突变体制备的幼虫提取物具有充分的配体活性。在这里，我们证明，Spz 5，蛋白质的Spz家族的成员，作为Toll-1受体的配体的功能。已知弗林蛋白酶对Spz 5的加工对于Spz 5至Toll-6的配体活性是重要的，但其对Toll-1受体的功能并不需要弗林蛋白酶对Spz 5的加工。通过产生spz 5无效突变体，我们进一步表明幼虫衍生提取物的Toll-1配体活性主要来自Spz 5。最后，我们发现spz和spz 5在发育过程中存在遗传互作。本研究鉴定了果蝇Toll-1受体的新配体，提供了Toll-1是一种多配体受体的证据，类似于哺乳动物Toll样受体。(C)2018作者爱思唯尔公司出版
The Drosophila Toll-1 receptor is involved in embryonic development, innate immunity, and tissue homeostasis. Currently, as a ligand for the Toll-1 receptor, only Spatzle (Spz) has been identified and characterized. We previously reported that Drosophila larva-derived tissue extract contains ligand activity for the Toll-1 receptor, which differs from Spz based on the observation that larval extract prepared from spz mutants possessed full ligand activity. Here, we demonstrate that Spz5, a member of the Spz family of proteins, functions as a ligand for the Toll-1 receptor. Processing of Spz5 by Furin protease, which is known to be important for ligand activity of Spz5 to Toll-6, is not required for its function to the Toll-1 receptor. By generating a spz5 null mutant, we further showed that the Toll-1 ligand activity of larva-derived extract is mainly derived from Spz5. Finally, we found a genetic interaction between spz and spz5 in terms of developmental processes. This study identified a novel ligand for the Drosophila Toll-1 receptor, providing evidence that Toll-1 is a multi-ligand receptor, similar to the mammalian Toll-like receptor. (C) 2018 The Authors. Published by Elsevier Inc.