The Drosophila melanogaster phospholipid flippase dATP8B is required for odorant receptor function.
The Drosophila melanogaster phospholipid flippase dATP8B is required for odorant receptor function.
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DOI：
10.1371/journal.pgen.1004209
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发表时间：
2014-03
期刊：
影响因子：
4.5
通讯作者：
Warr CG
中科院分区：
文献类型：
--
作者：
Liu YC;Pearce MW;Honda T;Johnson TK;Charlu S;Sharma KR;Imad M;Burke RE;Zinsmaier KE;Ray A;Dahanukar A;de Bruyne M;Warr CG
昆虫的嗅觉系统是其行为的各个方面的基础，并且昆虫嗅觉受体神经元（ORN）对广泛的环境线索表现出精致的特异性和敏感性。在黑腹果蝇中，ORN反应由三种不同的受体家族决定：气味受体（Or）、亲电离受体（IR）和味觉受体（Gr）。然而，这些不同受体家族的信号传导的确切机制尚未完全了解。在这里，我们报告了一个意想不到的发现，4型P型ATP酶磷脂转运蛋白dATP 8B，同源的蛋白质与肝内胆汁淤积症和听力损失的人，是至关重要的果蝇嗅觉反应。dATP 8B突变严重减弱气味检测的敏感性，特别是在OR表达的ORN，但不影响IR或Gr受体介导的反应。因此，我们发现dATP 8B在ORN中表达，并定位于嗅觉神经元的树突膜，在那里发生信号转导。或蛋白质的树突的本地化是不受影响的dATP 8B突变体，树突形态，而不是dATP 8B是至关重要的或信号。由于dATP 8B是ATP酶的磷脂翻转酶家族的成员，其功能是确定质膜的外小叶和内小叶之间的磷脂组成的不对称性，我们的研究结果表明，在化学受体蛋白的特定家族的信号传导中需要磷脂不对称性。昆虫的嗅觉系统对于寻找配偶、食物和寄主植物等关键行为至关重要。昆虫可以使用三种不同的嗅觉受体蛋白家族来检测广泛的环境线索。为什么昆虫有三个不同的受体基因家族，以及它们如何一起发挥作用，还没有完全弄清楚。在这里，我们确定了一个新的基因，dATP 8B，这是至关重要的，特别是需要在果蝇这些受体家族的功能之一。dATP 8B是P4型ATP酶或磷脂翻转酶的成员;这些酶的功能是在质膜的外小叶和内小叶之间建立脂质组成的差异或不对称性。这被认为是重要的许多细胞膜过程;然而，个别翻转酶蛋白的具体功能没有得到很好的描述。我们发现，dATP 8B是所需的气味受体家族的功能，但不是离子型和味觉受体家族。这进一步突出了这些受体家族之间的功能差异，并表明磷脂在特定受体蛋白家族的信号传导中的作用。
The olfactory systems of insects are fundamental to all aspects of their behaviour, and insect olfactory receptor neurons (ORNs) exhibit exquisite specificity and sensitivity to a wide range of environmental cues. In Drosophila melanogaster, ORN responses are determined by three different receptor families, the odorant (Or), ionotropic-like (IR) and gustatory (Gr) receptors. However, the precise mechanisms of signalling by these different receptor families are not fully understood. Here we report the unexpected finding that the type 4 P-type ATPase phospholipid transporter dATP8B, the homologue of a protein associated with intrahepatic cholestasis and hearing loss in humans, is crucial for Drosophila olfactory responses. Mutations in dATP8B severely attenuate sensitivity of odorant detection specifically in Or-expressing ORNs, but do not affect responses mediated by IR or Gr receptors. Accordingly, we find dATP8B to be expressed in ORNs and localised to the dendritic membrane of the olfactory neurons where signal transduction occurs. Localisation of Or proteins to the dendrites is unaffected in dATP8B mutants, as is dendrite morphology, suggesting instead that dATP8B is critical for Or signalling. As dATP8B is a member of the phospholipid flippase family of ATPases, which function to determine asymmetry in phospholipid composition between the outer and inner leaflets of plasma membranes, our findings suggest a requirement for phospholipid asymmetry in the signalling of a specific family of chemoreceptor proteins. The olfactory systems of insects are fundamental to critical behaviours such as finding mates, food and host plants. Insects can detect a wide range of environmental cues using three different families of olfactory receptor proteins. Why insects have three different families of receptor genes, and how they function together, is not fully understood. Here we identified a new gene, dATP8B, which is critically and specifically required for the function of only one of these receptor families in Drosophila. dATP8B is a member of the P4-type ATPases, or phospholipid flippases; these enzymes function in establishing a difference or asymmetry in lipid composition between the outer and inner leaflets of plasma membranes. This is thought to be important for many cellular membrane processes; however, specific functions of individual flippase proteins are not well described. We find that dATP8B is required for the function of the odorant receptor family, but not the ionotropic-like and gustatory receptor families. This further highlights the functional differences between these receptor families and suggests a role for phospholipids in the signalling of a specific family of receptor proteins.
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