Aminophospholipid Signaling in Olfactory Transduction

这项研究的长期目标是确定潜在的分子机制。 果蝇体内挥发性气味和信息素的检测这项工作意义重大，因为 昆虫将毁灭性的疾病传播给人类，它们利用嗅觉寻找寄主和配偶。 了解这些机制将有助于对其破坏采取新的方法。果蝇是一种优秀的 模型系统，揭示嗅觉的潜在机制，由于其丰富的遗传工具，包括无偏倚 基因筛查。我们最近发现了由磷脂酰丝氨酸(PS)转运酶介导的脂质转位 DATP8B，对于正常的气味敏感性是必不可少的。我们现在正在利用这一发现来确定 脂类转运的成分和途径及其与气味敏感性的关系。这部作品 代表了一条新的调查道路。 使用基因筛查，我们确定了一种蛋白激酶C，它与dATP8B在基因上相互作用，并出现 转导PS局部化的大部分效应。我们建议进行实验，以破译这种激酶是如何 影响嗅觉。目的1通过鉴定PKC98E在嗅觉中的定位，探讨其在嗅觉中的作用。 嗅神经元，并评估零和显性等位基因的表型来分析嗅觉 后果。目的2探讨OCCO中保守的PKC磷酸化位点在嗅觉中的作用 敏感性和受体运输，以及体内磷酸化是否依赖气味。目标3是 从35个预先选定的候选者中确定此过程中涉及的其他组件，以获得 对这一机制有了更全面的认识。这些目标的成功实现将显著 促进我们对昆虫嗅觉的理解，并可能对脂质的作用提供令人兴奋的见解 调制嗅觉信号转导中的转位。

The broad long-term objective of this research is to determine the molecular mechanisms underlying detection of volatile odorants and pheromones in Drosophila melanogaster. This work is significant because insects transmit devastating diseases to humans and they use olfaction to find hosts and mates. Understanding these mechanisms will facilitate new approaches for its disruption. Drosophila is an excellent model system to reveal mechanisms underlying olfaction due to its wealth of genetic tools, including unbiased genetics screens. We recently found lipid translocation, mediated by the phosphatidylserine (PS) flippase dATP8B, is essential for normal odorant sensitivity. We are now leveraging this discovery to identify the components and pathways underlying lipid translocation and its relation to odorant sensitivity. This work represents a new path of investigation. Using a genetic screen, we identified a protein kinase C that genetically interacts with dATP8B and appears to transduce most of the effects of PS localization. We propose experiments to decipher how this kinase impacts olfaction. Aim 1 is to explore the role of PKC98E in olfaction by characterizing its localization in olfactory neurons, and evaluating the phenotype of null and dominant alleles to analyze the olfactory consequences. Aim 2 explores the role of conserved PKC phosphorylation sites in ORCO on olfactory sensitivity and receptor trafficking, and whether phosphorylation is odorant-dependent in vivo. Aim 3 is to identify additional components involved in this process from a pool of 35 pre-selected candidates to gain a more complete understanding of this mechanism. Successful completion of these aims will significantly advance our understanding of insect olfaction and may provide exciting insights into the role of lipid translocation in modulating olfactory signal transduction.