Urotensin II in invertebrates: from structure to function in Aplysia californica.

Urotensin II in invertebrates: from structure to function in Aplysia californica.
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DOI:
10.1371/journal.pone.0048764
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Sweedler JV
Sweedler JV
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Romanova EV;Sasaki K;Alexeeva V;Vilim FS;Jing J;Richmond TA;Weiss KR;Sweedler JV

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神经肽是一种古老的信号分子,参与生物体内稳态和功能的许多方面。尾加压素II(UII)是一种具有一系列激素功能的肽,以前仅在脊椎动物中报道。在这里,我们提供了第一个直接的证据表明,UII样肽也存在于无脊椎动物,特别是海洋软体动物Auspsia californica。海兔中枢神经系统(CNS)中UII的存在意味着比脊椎动物更古老的基因谱系。使用代表性差异分析,我们确定了一种蛋白质前体的mRNA,编码一种预测的神经肽,我们命名为尾加压素II(apUII),与脊椎动物UII的序列和结构相似。原位杂交和免疫组织化学,我们映射的apUII mRNA及其激素原的表达在中枢神经系统和本地化的apUII样免疫反应颊感觉神经元和大脑A簇神经元。对单个分离的神经元进行质谱分析,并对分级肽提取物进行串联质谱分析,使我们能够定义apUII神经肽前体的翻译后加工,并确认成熟神经肽apUII的高度保守的环状性质。对合成apUII的中枢效应的电生理学分析表明,它在进食行为中的饱腹感和/或厌恶信号中起作用。在无脊椎动物模型的数值小的CNS中找到脊椎动物UII的同源物对于深入了解高等后生动物中介导UII生物活性的分子机制和途径是重要的。
Neuropeptides are ancient signaling molecules that are involved in many aspects of organism homeostasis and function. Urotensin II (UII), a peptide with a range of hormonal functions, previously has been reported exclusively in vertebrates. Here, we provide the first direct evidence that UII-like peptides are also present in an invertebrate, specifically, the marine mollusk Aplysia californica. The presence of UII in the central nervous system (CNS) of Aplysia implies a more ancient gene lineage than vertebrates. Using representational difference analysis, we identified an mRNA of a protein precursor that encodes a predicted neuropeptide, we named Aplysia urotensin II (apUII), with a sequence and structural similarity to vertebrate UII. With in-situ hybridization and immunohistochemistry, we mapped the expression of apUII mRNA and its prohormone in the CNS and localized apUII-like immunoreactivity to buccal sensory neurons and cerebral A-cluster neurons. Mass spectrometry performed on individual isolated neurons, and tandem mass spectrometry on fractionated peptide extracts, allowed us to define the posttranslational processing of the apUII neuropeptide precursor and confirm the highly conserved cyclic nature of the mature neuropeptide apUII. Electrophysiological analysis of the central effects of a synthetic apUII suggests it plays a role in satiety and/or aversive signaling in feeding behaviors. Finding the homologue of vertebrate UII in the numerically small CNS of an invertebrate animal model is important for gaining insights into the molecular mechanisms and pathways mediating the bioactivity of UII in the higher metazoan.
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