Cell Biology of Signaling Complexes in Phototransduction

光转导信号复合物的细胞生物学

• 批准号: 7127826
• 负责人: SUSAN L TSUNODA
• 金额: $ 3.7万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7127826
• 关键词: Drosophilidae; biological signal transduction; cell biology; confocal scanning microscopy; electron microscopy; gene expression; gene mutation; genetic screening; immunocytochemistry; mutant; photoconduction; protein protein interaction; receptor; southern blotting; transcription factor

DESCRIPTION (provided by applicant): An important issue in the field of signal transduction is how signaling molecules are organized into different pathways within the same cell. Our goal is to understand how the signal transduction cascade that underlies the phototransduction process is organized, and how individual components interact and participate in normal visual function. The importance of assembling signaling molecules into architecturally defined complexes has emerged as an essential cellular strategy to ensure speed and specificity of signaling. Results in Drosophila photoreceptors as well as in other systems and organisms have further demonstrated that the subcellular localization of these signaling complexes is essential for effective signaling. Mislocalization of signaling components is often the equivalent of their absence, and consequences can be severe. Critical questions that arise then are: how are signaling complexes targeted to the right subcellular domain? How and where are they assembled? How is this assembly regulated? How are they anchored or stabilized in the proper locale? This grant proposal focuses on a molecular-genetic dissection of the assembly and localization of signaling complexes in Drosophila photoreceptors. We will 1) perform a comprehensive genetic screen to isolate mutations affecting the proper localization of signaling complexes in photoreceptors, 2) characterize the mutants genetically, cell biologically, and physiologically, 3) isolate the defective genes, compare the homologous sequence from wild-type flies, identify the nature of the change, and introduce the wild-type gene back into flies and test for rescue of the phenotype, 4) for those genes that warrant further investigation, we will study how the proteins they encode function in assembly and localization processes. Components and strategies used in Drosophila are likely to be conserved in mammals. We expect to identify and characterize key components in the assembly, regulation of assembly, targeting, and anchoring of signaling complexes.

描述（由申请人提供）： 信号转导领域的一个重要问题是信号分子如何组织到同一细胞内的不同途径中。我们的目标是了解如何组织光转导过程的信号传输级联，以及单个组件如何相互作用并参与正常的视觉功能。将信号分子组装到结构定义的复合物中的重要性已成为确保信号传导速度和特异性的必不可少的细胞策略。果蝇感光体以及其他系统和生物的结果进一步证明，这些信号传导复合物的亚细胞定位对于有效信号传导至关重要。信号传导分量的错误定位通常相当于它们的缺失，后果可能很严重。然后出现的关键问题是：如何针对右亚细胞域的信号传导复合物？他们如何以及在哪里组装？该议会如何受到监管？它们如何锚定或稳定在适当的语言环境中？该赠款提案着重于果蝇感光体中信号复合物的组装和定位的分子遗传解剖。我们将1）执行全面的遗传筛选，以分离影响光感受器中信号传导复合物正确定位的突变，2）在遗传上，细胞上，生物学和生理学上表征突变体的特征，3）隔离缺陷的基因，比较了从野性变化的范围和范围的范围的范围，并将其引入野外的本质，并将其与野外的性质进行比较对于需要进一步研究的基因，我们将研究它们在组装和定位过程中的蛋白质如何编码功能。果蝇中使用的成分和策略可能在哺乳动物中保存。我们希望在组装，组装调节，靶向和锚定信号传导复合物中识别和表征关键组件。