Aminophospholipid Signaling in Olfactory Transduction

嗅觉转导中的氨基磷脂信号传导

• 批准号: 10055765
• 负责人: Dean P. Smith
• 金额: $ 34.08万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-01 至 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10055765
• 关键词: Affect; Alanine; Alleles; Biological Models; Bypass; CRISPR/Cas technology; Candidate Disease Gene; Cell membrane; Chromosomes; Cilia; Cues; Data; Defect; Dengue; Detection; Disease; Disease Vectors; Drosophila genus; Drosophila melanogaster; Environment; Family; Genes; Genetic; Genetic Screening; Human; Insecta; Investigation; Link; Lipids; Location; Malaria; Mediating; Molecular; Molecular Probes; Neurons; Nonhomologous DNA End Joining; Olfactory Pathways; PKC Phosphorylation Site; PRKCA gene; Partner in relationship; Pathway interactions; Phenotype; Pheromone; Phosphatidylserines; Phosphorylation; Phosphorylation Site; Phosphotransferases; Play; Process; Protein Family; Protein Isoforms; Protein Kinase C; RNA Interference; Regulation; Research; Role; Signal Transduction; Site; Smell Perception; Source; System; Testing; West Nile virus; Work; Yellow Fever; Zika Virus; arthropod-borne; desensitization; experimental study; extracellular; gene product; human disease; human morbidity; human mortality; in vivo; insight; knock-down; loss of function; member; mutant; novel; novel strategies; overexpression; receptor; response; tool; trafficking

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.

这项研究的广泛的长期目标是确定潜在的分子机制 果蝇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，它们利用嗅觉寻找宿主和配偶。 了解这些机制将有助于新的方法来破坏它。果蝇是一种优秀的 模型系统，以揭示嗅觉的机制，由于其丰富的遗传工具，包括无偏 基因筛查我们最近发现了由磷脂酰丝氨酸（PS）翻转酶介导的脂质易位 dATP 8B是正常气味敏感性所必需的。我们现在正在利用这一发现来确定 脂质移位的潜在成分和途径及其与气味敏感性的关系。这项工作 代表了一条新的调查途径 使用遗传筛选，我们鉴定了一种蛋白激酶C，它与dATP 8B发生遗传相互作用， 以转换PS定位的大部分影响。我们提出实验来解释这种激酶 影响嗅觉。目的：1.通过研究PKC 98 E在嗅觉中的定位，探讨PKC 98 E在嗅觉中的作用。 嗅觉神经元，并评估无效和显性等位基因的表型，以分析嗅觉神经元， 后果目的2探讨ORCO中保守的PKC磷酸化位点在嗅觉神经元中的作用。 敏感性和受体运输，以及磷酸化是否在体内依赖于气味。目标3是 从35个预选候选人中确定参与这一进程的其他组成部分， 更全面地了解这一机制。这些目标的成功实现将大大 推进我们对昆虫嗅觉的理解，并可能为脂质的作用提供令人兴奋的见解 易位调节嗅觉信号转导。

项目成果

Correction: Odorant Responses and Courtship Behaviors Influenced by at4 Neurons in Drosophila.

纠正：果蝇中 at4 神经元影响的气味反应和求爱行为。

• DOI: 10.1371/journal.pone.0190805
• 发表时间: 2018
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Pitts,Svetlana;Pelser,Elizabeth;Meeks,Julian;Smith,Dean
• 通讯作者: Smith,Dean

A broadly tuned odorant receptor in neurons of trichoid sensilla in locust, Locusta migratoria.

蝗虫毛状感觉器神经元中广泛调节的气味受体

• DOI: 10.1016/j.ibmb.2016.10.008
• 发表时间: 2016-12
• 期刊: Insect biochemistry and molecular biology
• 影响因子: 3.8
• 作者: You Y;Smith DP;Lv M;Zhang L
• 通讯作者: Zhang L

Odorant Receptor Desensitization in Insects.

• DOI: 10.1177/1179069517748600
• 发表时间: 2017
• 期刊: Journal of experimental neuroscience
• 作者: Guo H;Smith DP
• 通讯作者: Smith DP

Recent Insights into Insect Olfactory Receptors and Odorant-Binding Proteins.

• DOI: 10.3390/insects13100926
• 发表时间: 2022-10-13
• 期刊: Insects
• 影响因子: 3