Characterization and distribution of NKD, a receptor for Drosophila tachykinin-related peptide 6
Characterization and distribution of NKD, a receptor for Drosophila tachykinin-related peptide 6
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DOI：
10.1016/j.peptides.2008.10.012
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发表时间：
2009-03-01
期刊：
影响因子：
3
通讯作者：
Nassel, Dick R.
中科院分区：
文献类型：
--
作者：
Poels, Jeroen;Birse, Ryan T.;Nassel, Dick R.
与脊椎动物速激肽相关的神经肽已在果蝇中被发现，并被称为Drosotachykinins，或DTK。两个果蝇G蛋白偶联受体，命名为NKD(果蝇神经激肽受体；CG6515)和DTKR(果蝇速激肽受体；CG7887)，显示出与哺乳动物速激肽受体相似的序列。而DTKR被DTKs(Birse RT、Johnson EC、Taghert PH、Nassel Dr.)激活，广泛分布的果蝇G蛋白偶联受体(CG7887)被内源性速激肽相关肽激活。神经生物学杂志2006；66：33-46；Poels J，Verlinden H，Fichna J，Van Loy T，Franssens V，Studzian K等人。两种进化保守的昆虫神经激肽样受体的功能比较。多肽2007；28：103-8]，并通过免疫细胞化学定位于果蝇中枢神经系统(CNS)，但NKD的激动剂依赖的激活和分布尚未得到深入研究。在本研究中，我们用果蝇神经肽文库挑战表达NKD的哺乳动物和昆虫细胞，并发现DTK-6是一种特异性激动剂，可以在这些细胞中诱导钙反应。此外，我们还制备了针对NKD蛋白序列的抗血清，以分析受体的分布。我们发现NKD在中枢神经系统中的分布没有DTKR丰富，只有NKD在肠道中发现。事实上，这两种受体在中枢神经系统中以相互排斥的方式分布。受体在脑神经毛膜中的分布与DTK的分布相一致。最有趣的是，NKD似乎只被DTK-6激活，DTK-6已知在其他保守的C末端核心基序中具有Ala取代。我们的发现表明，NKD和DTKR为两个功能和空间上分离的多肽信号系统提供了底物。(C)2008 Elsevier Inc.保留所有权利。
Neuropeptides related to vertebrate tachykinins have been identified in Drosophila and are referred to as drosotachykinins, or DTKs. Two Drosophila G protein-coupled receptors, designated NKD (neurokinin receptor from Drosophila; CG6515) and DTKR (Drosophila tachykinin receptor; CG7887), display sequence similarities to mammalian tachykinin receptors. Whereas DTKR was shown to be activated by DTKs (Birse RT, Johnson EC, Taghert PH, Nassel DR. Widely distributed Drosophila G-protein-coupled receptor (CG7887) is activated by endogenous tachykinin-related peptides. J Neurobiol 2006;66:33-46; Poels J, Verlinden H, Fichna J, Van Loy T, Franssens V, Studzian K, et al. Functional comparison of two evolutionary conserved insect neurokinin-like receptors. Peptides 2007;28:103-8] and was localized by immunocytochemistry in Drosophila central nervous system (CNS), agonist-dependent activation and distribution of NKD have not yet been investigated in depth. In the present study, we have challenged NKD-expressing mammalian and insect cells with a library of Drosophila neuropeptides and discovered DTK-6 as a specific agonist that can induce a calcium response in these cells. in addition, we have produced antisera to sequences from NKD protein to analyze receptor distribution. We found that NKD is less abundantly distributed in the central nervous system than DTKR, and only NKD was found in the intestine. In fact, the two receptors are distributed in mutually exclusive patterns in the CNS. The combined distribution of the receptors in brain neuropils corresponds well with the distribution of DTKs. Most interestingly, NKD appears to be activated only by DTK-6, known to possess an Ala-substitution in an otherwise conserved C-terminal core motif. our findings suggest that NKD and DTKR provide substrates for two functionally and spatially separated peptide signaling systems. (c) 2008 Elsevier Inc. All rights reserved.