Insect odorant receptor trafficking requires calmodulin.
Insect odorant receptor trafficking requires calmodulin.
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DOI：
10.1186/s12915-016-0306-x
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发表时间：
2016-09-29
期刊：
影响因子：
5.4
通讯作者：
Jones WD
中科院分区：
文献类型：
--
作者：
Bahk S;Jones WD
像大多数动物一样，昆虫依靠嗅觉系统寻找食物和配偶，并避免有毒化学物质和捕食者。大多数昆虫嗅觉神经元表达气味特异性气味受体（OR）沿着嗅觉辅助受体Orco。Orco结合OR并允许它们运输到触角嗅觉感觉神经元（OSN）的树突，在那里它们一起被建议形成异聚配体门控的非选择性阳离子通道。虽然Orco中的大多数氨基酸残基在昆虫目中是非常保守的，但Orco的第二胞内环中的一个特别保守的区域是推定的钙调蛋白（CaM）结合位点（CBS）。在本研究中，我们探讨了Orco和钙调素在果蝇嗅觉神经元中的关系。我们首先发现OSN特异性敲低的钙调素在OSN发展的开始破坏了自发放电的OSN和减少Orco贩运的纤毛树突的OSN，而不影响他们的形态。然后，我们产生了一系列Orco CBS突变蛋白，并发现它们都不能拯救Orco无效的Orco 1突变表型，其特征是OR蛋白运输缺陷，从而阻止自发和气味诱发的OSN活性。与同样构建的野生型Orco相比，所有Orco CBS突变体都卡在OSN索马中，阻止了甚至最小的气味诱发反应。最后，我们发现CaM对OR运输的调节依赖于活性。在所有Orco阳性OSN中，在OR表达良好建立后，敲低CaM对嗅觉反应性的影响很小。然而，当与长期暴露于气味剂相结合时，这种迟发性CaM敲低显著降低了嗅觉敏感性和Orco仅向响应于暴露的气味剂的OSN的纤毛树突的贩运。在这项研究中，我们表明钙调素调节或贩运和嗅觉反应在体内果蝇嗅觉神经元通过一个保守的结合位点的嗅觉辅助受体Orco。由于钙调素的调节Orco似乎是依赖于活动，我们提出了一个模型，在该模型中的钙调素/Orco相互作用，使昆虫OSNs保持适当的树突水平的OR，无论环境中的气味浓度。
Like most animals, insects rely on their olfactory systems for finding food and mates and in avoiding noxious chemicals and predators. Most insect olfactory neurons express an odorant-specific odorant receptor (OR) along with Orco, the olfactory co-receptor. Orco binds ORs and permits their trafficking to the dendrites of antennal olfactory sensory neurons (OSNs), where together, they are suggested to form heteromeric ligand-gated non-selective cation channels. While most amino acid residues in Orco are well conserved across insect orders, one especially well-conserved region in Orco’s second intracellular loop is a putative calmodulin (CaM) binding site (CBS). In this study, we explore the relationship between Orco and CaM in vivo in the olfactory neurons of Drosophila melanogaster. We first found OSN-specific knock-down of CaM at the onset of OSN development disrupts the spontaneous firing of OSNs and reduces Orco trafficking to the ciliated dendrites of OSNs without affecting their morphology. We then generated a series of Orco CBS mutant proteins and found that none of them rescue the Orco-null Orco1 mutant phenotype, which is characterized by an OR protein trafficking defect that blocks spontaneous and odorant-evoked OSN activity. In contrast to an identically constructed wild-type form of Orco that does rescue the Orco1 phenotype, all the Orco CBS mutants remain stuck in the OSN soma, preventing even the smallest odorant-evoked response. Last, we found CaM’s modulation of OR trafficking is dependent on activity. Knock-down of CaM in all Orco-positive OSNs after OR expression is well established has little effect on olfactory responsiveness alone. When combined with an extended exposure to odorant, however, this late-onset CaM knock-down significantly reduces both olfactory sensitivity and the trafficking of Orco only to the ciliated dendrites of OSNs that respond to the exposed odorant. In this study, we show CaM regulates OR trafficking and olfactory responses in vivo in Drosophila olfactory neurons via a well-conserved binding site on the olfactory co-receptor Orco. As CaM’s modulation of Orco seems to be dependent on activity, we propose a model in which the CaM/Orco interaction allows insect OSNs to maintain appropriate dendritic levels of OR regardless of environmental odorant concentrations.
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影响因子：
9.8
作者：
Benton, Richard;Sachse, Silke;Michnick, Stephen W;Vosshall, Leslie B
通讯作者：
Vosshall, Leslie B
影响因子：
16.2
作者：
Dobritsa, AA;van der Goes van Naters, W;Carlson, JR
通讯作者：
Carlson, JR
DOI：
10.1073/pnas.0712033105
发表时间：
2008-08-26
影响因子：
11.1
作者：
Lee, Jeong Ho;Lee, Jinu;Roche, Katherine W.
通讯作者：
Roche, Katherine W.
DOI：
10.1093/bioinformatics/bts199
发表时间：
2012-06-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Kearse M;Moir R;Wilson A;Stones-Havas S;Cheung M;Sturrock S;Buxton S;Cooper A;Markowitz S;Duran C;Thierer T;Ashton B;Meintjes P;Drummond A
通讯作者：
Drummond A
影响因子：
16.2
作者：
Larsson, MC;Domingos, AI;Vosshall, LB
通讯作者：
Vosshall, LB